Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on pho...Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Dear Editor,We are writing to present a case of bilateral sequential cytomegalovirus retinitis(CMVR)in a patient with dyskeratosis congenita(DC).DC is an inherited bone marrow failure syndrome characterized by a typic...Dear Editor,We are writing to present a case of bilateral sequential cytomegalovirus retinitis(CMVR)in a patient with dyskeratosis congenita(DC).DC is an inherited bone marrow failure syndrome characterized by a typical diagnostic triad of oral leukoplakia,nail dystrophy,and reticular hyperpigmentation[1].DC can be inherited in one of the three forms,X-linked,autosomal dominant,and autosomal recessive.展开更多
Retinitis pigmentosa(RP)is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium(RPE)cells.Its main clinical manifestations include night blindness and...Retinitis pigmentosa(RP)is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium(RPE)cells.Its main clinical manifestations include night blindness and progressive loss of peripheral vision,making it a prevalent debilitating eye disease that significantly impacts patients’quality of life.RP exhibits significant phenotypic and genetic heterogeneity.For instance,numerous abnormal genes are implicated in RP,resulting in varying clinical presentations,disease progression rates,and pathological characteristics among different patients.Consequently,gene therapy for RP poses challenges due to these complexities.However,stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem cells.In recent years,a large number of animal experiments and clinical trials based on stem cell transplantation attempts,especially cord blood mesenchymal stem cell(MSC)transplantation and bone marrow-derived MSC transplantation,have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected eye.However,stem cell therapy also has certain limitations,such as the fact that RP patients may involve multiple types of retinal cytopathia,which brings great challenges to stem cell transplantation therapy,and further research is needed to solve various problems faced by this approach in the clinic.Through comprehensive analysis of the etiology and histopathological changes associated with RP,this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials,while also highlighting the existing limitations that warrant further investigation.展开更多
Aim: To report a familial case of syndromic retinitis pigmentosa identified at Aristide Le Dantec Hospital in Dakar and to describe their clinical characteristics ophthalmic. Observation: We report a sibling group of ...Aim: To report a familial case of syndromic retinitis pigmentosa identified at Aristide Le Dantec Hospital in Dakar and to describe their clinical characteristics ophthalmic. Observation: We report a sibling group of nine children, four died at a young age from unknown causes. Three children were affected by retinitis pigmentosa, two cases were syndromic. A history of nyctalopia was found in all three affected children. The mean age of onset of decreased visual acuity was 6.6 years. Patient 1 affected by syndromic retinitis pigmentosa had an extraocular sign of cystic dilation of the main bile duct. Patient 2 had myoclonic epilepsy, psychomotor retardation, and the molar tooth sign on cerebral MRI (highly suggestive of Joubert syndrome). The third child had isolated retinitis pigmentosa. Ophthalmological examinations (fundus examination, electroretinogram, and visual evoked potentials) and pediatric examinations in the remaining two children were normal. Discussion and Conclusion: Retinitis pigmentosa is a rare degenerative disease that can be associated with several other malformations, highlighting the importance of screening for associated conditions. It presents a grim functional prognosis and a life prognosis dependent on extraocular manifestations. Molecular biology (karyotyping, next-generation sequencing) could have identified the implicated genes and allowed for a formal diagnosis and genetic counseling.展开更多
AIM:To characterize the ophthalmic clinical phenotype of a family with retinitis pigmentosa(RP)and closed-angle glaucoma and to detect pathogenic genes and mutation sites causing RP in this family.METHODS:Ophthalmic c...AIM:To characterize the ophthalmic clinical phenotype of a family with retinitis pigmentosa(RP)and closed-angle glaucoma and to detect pathogenic genes and mutation sites causing RP in this family.METHODS:Ophthalmic clinic performance was examined in detail in 8 enrolled family members.Genomic DNA was extracted from the peripheral blood of 4 family members for whole-exome sequencing(WES)to select potential genetic mutations whose structures were identified by bioinformatics analysis.Then,Sanger sequencing was used in 12 family members and control group members to validate and confirm the disease-causing mutation loci,and we analyzed the genotype-phenotype relationships.RESULTS:The known c.512C>T(p.P171L)mutation in the rhodopsin(RHO)gene was only found in afflicted family members and was confirmed by WES and Sanger sequencing as the pathogenic mutation in this family.In addition to being diagnosed with RP,family member III:4 was found to have bilateral closed-angle glaucoma,high myopia,and concurrent cataracts,and family members II:2 and II:4 had pathological changes of anterior chamber angle narrowing.Family members IV:3 and IV:4 were found to have retinoschisis.CONCLUSION:Glaucoma and related pathological changes,such as retinoschisis,in family members are preliminarily considered RP complications caused by RHO mutation.展开更多
AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic ex...AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic examinations including best corrected visual acuity,fundus photography,vision field,and pattern-visual evoked potential were performed to identify the disease phenotype of a six-yearold boy from the family(proband).Genomic DNA was extracted from peripheral blood of five available members of the pedigree.Whole-exome sequencing(WES),Sanger sequencing,and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR.Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants.RESULTS:The proband was diagnosed as having retinitis pigmentosa(RP).He had severe symptoms with early onset.A novel splicing mutation,c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing.Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped,leading to the subsequent deletion of 623 correct amino acids(c.529_619del p.Val177Glnfs*16).CONCLUSION:We identify a novel splice donor site mutation causing aberrant splicing of RPGR.Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.展开更多
Aim: To establish a useful and objective classification for retinitis pigmentosa (RP) to evaluate the disease severity. Methods: This is a retrospective cross-sectional study. Visual acuity (VA), visual field (VF) wid...Aim: To establish a useful and objective classification for retinitis pigmentosa (RP) to evaluate the disease severity. Methods: This is a retrospective cross-sectional study. Visual acuity (VA), visual field (VF) width, ellipsoid zone width on optic cohorence tomography (OCT) and multifocal electroretinography (mf ERG) values were obtained from medical records of patients with RP. A scoring criterion was developed wherein each variable was assigned a score from 0 to 5 depending on its distribution. The cumulative score (from 0 to 20) was used to classify disease severity from grade 0 to 5. The scores were correlated with each other and the final grade. Results: Data of 152 eyes of 92 patients who had the results of all tests were reviewed. The mean age was 41.2 years. The mean VA of the patients was 0.13 ± 0.16 Snellen lines. The majority of patients had a VA less than 20/40 (88.6%), a visual field smaller than 20<sup>˚</sup> (78%), and an ellipsoid zone width smaller than 7<sup>˚</sup> (84.4%). The majority of the patients (85.4%) were in advanced stage of the disease (Grade 4 and 5). Conclusions: We present a simple, objective and easy to use disease severity classification for RP which can be used to categorize patients and to evaluate and compare treatment results.展开更多
AIMTo make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology.
AIM: To identify mutations with whole exome sequencing(WES) in a Chinese X-linked retinitis pigmentosa(XLRP) family. METHODS: Patients received the comprehensive ophthalmic evaluation. Genomic DNA was extracted from p...AIM: To identify mutations with whole exome sequencing(WES) in a Chinese X-linked retinitis pigmentosa(XLRP) family. METHODS: Patients received the comprehensive ophthalmic evaluation. Genomic DNA was extracted from peripheral blood and subjected to Sure Select Human All Exon 6+ UTR exon capture kit. The exons were sequenced as 100 base paired reads on Illumina HiS eq2500 system. Only mutations that resulted in a change in amino acid sequence were selected. A pattern of inheritance of the RP family was aligned to identified causal mutation.RESULTS: We analysed the data of WES information from XLRP family. The analysis revealed a hemizygous large genomic deletion of RPGR c.29113 del was responsible for this XLRP. The gross deletion lead to a frame-shift mutation and generate stop codon at 7 animo acid behind Asp(D10 Afs*7), which would serious truncate RPGR protein. The novel frame-shift mutation was found to segregate with retinitis pigmentosa(RP) phenotype in this family. Bilateral myopia was present on the male patients, but carrier female showed unilateral myopia without RP.CONCLUSION: Our study identifies a novel frame-shift mutation of RPGR in a Chinese family, which would expand the spectrum of RPGR mutations. The geno-phenotypic analysis reveals a correlation between RP and myopia. Although exact mechanism of RP related myopia is still unknown, but the novel frame-shift mutation will give our hit on studying the molecular pathogenesis of RP and myopia.展开更多
AIM：To compare the effectiveness between multiple intravitreal injections of ganciclovir alone and combined with foscarnet as initial treatment for patients with newlyonset cytomegalovirus retinitis （CMVR）.METHODS...AIM：To compare the effectiveness between multiple intravitreal injections of ganciclovir alone and combined with foscarnet as initial treatment for patients with newlyonset cytomegalovirus retinitis （CMVR）.METHODS：The retrospective study observed 37 patients（58 eyes） who suffered from CMVR onset between 2013 and 2015. Among them, 35 eyes underwent 4 weekly intravitreal injections of 3.0 mg ganciclovir, and 23 eyes underwent 4 weekly injections of 3.0 mg ganciclovir combined with 2.4 mg foscarnet. Visual acuity, intraocular pressure and viral load of cytomegalovirus （CMV） in aqueous humor measured by real-time polymerase chain reaction were compared before and after each injection.RESULTS：CMV-DNA copies in aqueous humor decreased remarkably in both groups. The average of CMV-DNA copies in patients’ aqueous decreased from 38.3×10~4 copies/mL at baseline to 2.2×10~4 copies/mL after the 4^（th） injection in patients who were treated with ganciclovir monotherapy,and decreased from 76.9×10~4 copies/mL to 11.3×10~4 copies/mL after 4 continuous injections of ganciclovir combined with foscarnet. No significant difference was found in reduction of viral load, change of visual acuities or intraocular pressures between monotherapy or combined therapy.CONCLUSION：Results of this study show that the initial effectiveness of treating CMVR after 4 weekly intravitreal injections is not significantly different from ganciclovir alone or combined with foscarnet. Continuous injection of ganciclovir alone is sufficient in treating immunosuppressive patients with newly-onset CMVR.展开更多
Retinitis pigmentosa（RP）is a group of heterogeneous inherited retinal diseases that is characterized by primary death rod photoreceptors and the secondary loss of cones.The degeneration of cones causes gradual const...Retinitis pigmentosa（RP）is a group of heterogeneous inherited retinal diseases that is characterized by primary death rod photoreceptors and the secondary loss of cones.The degeneration of cones causes gradual constriction of visual fields,leaving the central islands that are eventually snuffed out.Studies indicate that the hyperoxia causes oxidative damage in the retina and contributes to the cone death of RP.Moreover,abundant reactive oxidative species（ROS）which are generated in cones may result in mitochondria membrane depolarization,which has been ascribed a central role in the apoptotic process and has been proposed to act as a forward feeding loop for the activation of downstream cascades.Anthocyanin is a potent antioxidant which has been evidenced to be able to counteract oxidative damages,scavenge surplus ROS,and rectify abnormities in the apoptotic cascade.Taken together with its ability to attenuate inflammation which also contributes to the etiology of RP,it is reasonable to hypothesize that the anthocyanin could act as a novel therapeutic strategy to retard or prevent cone degeneration in RP retinas,particularly if the treatment is timed appropriately and delivered efficiently.Future pharmacological investigations will identify the anthocyanin as an effective candidate for PR therapy and refinements of that knowledge would ignite the hope of restoring the visual function in RP patients.展开更多
AIM：To compare the clinical manifestation of cytomegalovirus（CMV）retinitis and microvascular retinopathy（MVR）in patients with acquired immunodeficiency syndrome（AIDS）in China.METHODS：A total of 93 consecutive ...AIM：To compare the clinical manifestation of cytomegalovirus（CMV）retinitis and microvascular retinopathy（MVR）in patients with acquired immunodeficiency syndrome（AIDS）in China.METHODS：A total of 93 consecutive patients with AIDS,including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed.Highly active antiretroviral therapy（HAART）status was recorded.HIV and CMV immunoassay were also tested.CD4＋T-lymphocyte count and blood CMV-DNA test were performed in all patients.Aqueous humor CMV-DNA test was completed in 39patients.Ophthalmological examinations including best corrected visual acuity（BCVA,by International Standard Vision Chart）,intraocular pressure（IOP）,slit-lamp biomicroscopy,indirect ophthalmoscopy were performed.RESULTS：In MVR group,the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13.Blood CMV-DNA was 0（0,269 000）and 42 patients（80.77%）did not receive HAART.In CMV retinitis group,13 patients（31.71%）had anterior segment abnormality.The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470（0,1 450 000）.Nineteen patients（46.34%）had not received HAART.MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%,respectively.Two patients with MVR progressed to CMV retinitis during the follow-up period.CONCLUSION：In comparison of CMV,patients with MVR have relatively mild visual function impairment.Careful ophthalmological examination and close follow-up are mandatory,especially for patients who have systemic complications,positive CMV-DNA test and without received HAART.展开更多
AIM: To detect the pathogenetic mutations responsible for nonsyndromic autosomal recessive retinitis pigmentosa(RP) in 2 nonconsanguineous Chinese families. METHODS: The clinical data, including detailed medical histo...AIM: To detect the pathogenetic mutations responsible for nonsyndromic autosomal recessive retinitis pigmentosa(RP) in 2 nonconsanguineous Chinese families. METHODS: The clinical data, including detailed medical history, best corrected visual acuity(BCVA), slit-lamp biomicroscope examination, fundus photography, optical coherence tomography, static perimetry, and full field electroretinogram, were collected from the members of 2 nonconsanguineous Chinese families preliminarily diagnosed with RP. Genomic DNA was extracted from the probands and other available family members;wholeexome sequencing was conducted with the DNA samples provided by the probands, and all mutations detected by whole-exome sequencing were verified using Sanger sequencing in the probands and the other available family members. The verified novel mutations were further sequenced in 192 ethnicity matched healthy controls.RESULTS: The patients from the 2 families exhibited the typical symptoms of RP, including night blindness and progressive constriction of the visual field, and the fundus examinations showed attenuated retinal arterioles, peripheral bone spicule pigment deposits, and waxy optic discs. Whole-exome sequencing revealed a novel nonsense mutation in FAM161 A(c.943 A>T, p.Lys315*) and compound heterozygous mutations in RP1 L1(c.56 C>A, p.Pro19 His;c.5470 C>T, p.Gln1824*). The nonsense c.5470 C>T, p.Gln1824* mutation was novel. All mutations were verified by Sanger sequencing. The mutation p.Lys315* in FAM161A co-segregated with the phenotype, and all the nonsense mutations were absent from the ethnicity matched healthy controls and all available databases.CONCLUSION: We identify 2 novel mutations in genes responsible for autosomal recessive RP, and the mutation in FAM161A is reported for the first time in a Chinese population. Our result not only enriches the knowledge of the mutation frequency and spectrum in the genes responsible for nonsyndromic RP but also provides a new target for future gene therapy.展开更多
Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury,whereby it can inhibit microglial neurotoxicity.Therefore,luteolin holds the potential to be useful fo...Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury,whereby it can inhibit microglial neurotoxicity.Therefore,luteolin holds the potential to be useful for treatment of retinal diseases.The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on rod cells in rd10 mice,a slow photoreceptor-degenerative model of retinitis pigmentosa.Luteolin(100 mg/kg)intraperitoneally injected daily from postnatal day 14(P14)to P25 significantly enhanced the visual performance and retinal light responses of rd10 mice at P25.Moreover,it increased the survival of photoreceptors and improved retinal structure.Mechanistically,luteolin treatment attenuated increases in reactive oxygen species,photoreceptor apoptosis,and reactive gliosis;increased mRNA levels of anti-inflammatory cytokines while lowering that of pro-inflammatory and chemoattractant cytokines;and lowered the ratio of phospho-JNK/JNK.Application of the JNK inhibitor SP600125 exerted a similar protective effect to luteolin,suggesting that luteolin delays photoreceptor degeneration and functional deterioration in rd10 mice through regulation of retinal oxidation and inflammation by inhibiting the JNK pathway.Therefore,luteolin may be useful as a supplementary treatment for retinitis pigmentosa.This study was approved by the Qualified Ethics Committee of Jinan University,China(approval No.IACUC-20181217-02)on December 17,2018.展开更多
The effect of intravitreal ganciclovir injection combined with intravenous infusion on acquired immune deficiency syndrome(AIDS) patients with cytomegalovirus retinitis(CMVR) was investigated. A total of 32 eyes in 23...The effect of intravitreal ganciclovir injection combined with intravenous infusion on acquired immune deficiency syndrome(AIDS) patients with cytomegalovirus retinitis(CMVR) was investigated. A total of 32 eyes in 23 AIDS patients diagnosed as CMVR from 2017 to 2018 were included in the retrospective study. All patients underwent induction therapy by using intravenous drip of the anticytomegalovirus(CMV) agent ganciclovir(5 mg/kg q12 h) combined with intravitreal ganciclovir injection(3 mg/time, 2 times/wk). The visual acuity, fundus photographs, lesion location, and number of intravitreal injections were observed preoperatively and postoperatively. Totally 14 eyes were cured during induction therapy. The number of injections [4.13(2 to 6)] in CMVR patients with peripherally fundus lesions were significantly lower than those with central lesions (4.89(2 to 6))The individualized therapy of intravitreal ganciclovir injections for AIDS patients with CMVR can effectively reduce the numbers of intravitreal injections.展开更多
Objective To evaluate the prevalence of rhodopsin (RHO) mutations and the genotype-phenotype relationships in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) by conformation sensitive gel electrop...Objective To evaluate the prevalence of rhodopsin (RHO) mutations and the genotype-phenotype relationships in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) by conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing. Methods We have screened the five coding exons and splice sites of RHO gene in 27 probands who had no relativity from Chinese ADRP families and 100 normal controls to identify disease-associated mutations, using CSGE and direct DNA sequencing. Family members of some probands with disease-associated mutations were also genotyped to determine whether the RHO mutations segregated with retinitis pigmentosa (RP) in their families. Results Two RHO mutations, Pro347Leu and Pro327 (1-bp del), were identified separately in two families, thus the frequency of RHO mutations among this set of Chinese ADRP families is about 7.4% (2/27). Pro347Leu mutation was found in one ADRP proband as well as three her children who also had RP. She had relatively early onset at about 17 years. The only one child without this mutation had no symptom or sign of RP at age of 34. Pro327 (1-bp del) was identified in a late-onset ADRP patient, who appeared night blindness around 30 years old and in her fifties electroretinogram (ERG) has been flat in both scotopic and photopic phases. Family analysis showed that this mutation also existed in her younger dau-ghter and her elder sister, both of them also had RP. Three other family members were genotypically and phenotypically normal. Neither of the two mutations was detected in 100 normal controls.Conclusions The frequency of RHO mutations in Chinese patients was lower than that in Europe and North America. The phenotype of the patients with Pro347Leu corresponded to type 1 ADRP, with severe rod degeneration and some cone preservation later, while the phenotype of the patients carrying Pro327 (1-bp del) corresponded to type 2 ADRP, with a concomitant loss of rod and cone visual function. CSGE was found to be a sensitive, simple, and practical method for the screening of a large number of samples under highly reproducible conditions, and could be utilized in routine molecular diagnostic laboratories.展开更多
Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration.There is currently no effective treatment for retinitis pigmentosa.Although a mixture of lutein and other antioxidant agents has sh...Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration.There is currently no effective treatment for retinitis pigmentosa.Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration,the role of lutein alone remains unclear.In this study,we administered intragastric lutein to Pde6brd10 model mice,which display degeneration of retinal photoreceptors,on postnatal days 17(P17)to P25,when rod apoptosis reaches peak.Lutein at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle control.Lutein increased rhodopsin expression in rod cells and opsin expression in cone cells,in line with an increased survival rate of photoreceptors.Functionally,lutein improved visual behavior,visual acuity,and retinal electroretinogram responses in Pde6brd10 mice.Mechanistically,lutein reduced the expression of glial fibrillary acidic protein in Müller glial cells.The results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory effects.This study was approved by the Laboratory Animal Ethics Committee of Jinan University(approval No.LACUC-20181217-02)on December 17,2018.展开更多
AIM:To investigate the efficacy and the safety of umbilical cord derived mesenchymal stem cell(UC-MSC)implantation in patients with retinitis pigmentosa(RP).METHODS:This prospective,single-center,phase 3 clinical stud...AIM:To investigate the efficacy and the safety of umbilical cord derived mesenchymal stem cell(UC-MSC)implantation in patients with retinitis pigmentosa(RP).METHODS:This prospective,single-center,phase 3 clinical study enrolled 124 eyes of 82 RP patients.The patients received 5 million UC-MSCs to the suprachoroidal area with a surgical procedure.Patients were evaluated on the 1st day,1st,and 6th months postoperatively.Best corrected visual acuity(BCVA),anterior segment and fundus examinations,color photography,optical coherence tomography(OCT),and visual field(VF)tests were carried out at each visit.Fundus fluorescein angiography(FFA)and multifocal electroretinography(mfERG)recordings were performed at the end of the 6th month.Ocular and systemic adverse events of the surgical procedure were also noted.RESULTS:All of the 82 patients completed the 6-month follow-up period.None of them had any serious systemic or ocular complications.There were statistically significant improvements in BCVA and VF during the study(all P<0.05).The amplitudes of the P1 waves in the central areas showed significant improvements in mfERG recordings.There were also significant increases in implicit times of P1 waves in the central areas.CONCLUSION:Suprachoroidal administration of UC-MSCs has beneficial effect on BCVA,VF,and mfERG measurements during the 6-month follow-up period.Cell mediated therapy based on the secretion of growth factors(GFs)seems to be an effective and safe option for degenerative retinal diseases.展开更多
Retinitis pigmentosa(RP) is a commonly inherited disease of the retina, which is characterized by progressive loss of visual function due to specific genetic mutations. There are many risk factors that may have effect...Retinitis pigmentosa(RP) is a commonly inherited disease of the retina, which is characterized by progressive loss of visual function due to specific genetic mutations. There are many risk factors that may have effect on the progression of RP, such as inheritance patterns, genotype, gender, age, smoking, physical activity, and other demographic and environmental factors. Baseline visual field conditions, changes of ellipsoid zone, photoreceptor layer thickness, and choroidal structure are reported to be the phenotype risk factors for RP progression. Moreover, aqueous flare and high-sensitivity C-reactive protein are probable inflammation biomarkers for assessing the progression of RP. Increased oxidative stress is considered to be one of the potential factors for the existence of RP. The risk factors can be combined to form a corresponding prediction model to predict disease progression. This review is to summarize the current literature that studies the genetic, environmental, phenotypic, demographic, inflammatory and other risk factors of RP progression and discuss the most reliable risk factors that could provide predictive models.展开更多
基金supported by The Norwegian Research CouncilDepartment of Ophthalmology,Oslo University Hospital,Oslo,Norway(to TPU)+10 种基金Department of Medical Biochemistry,Oslo University Hospital,Oslo,Norway(to TPU)The Norwegian Association for the Blind and Partially Sighted(to TPU)The Ministry of Science and Technology of Taiwan,China MOST 105-2917-I-002-031,MOST 109-2917-I-564-032(to KC)The Scientific and Technological Research Council of Turkiye-TUBITAK(to KG)BrightFocus Foundation(to KSC)the Massachusetts Lions Foundation(to KSC)National Eye Institute Grant EY031696(to DFC)Harvard NeuroDiscovery Center Grant(to DFC)Department of Defense(USA)HT9425-23-1-1045(to DFC and AL)Core Grant for Vision Research from NIH/NEI to the Schepens Eye Research Institute(P30EY003790)South-Eastern Norway Regional Health Authority and the Norwegian Society of the Blind(to TPU).
文摘Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金Supported by grants from the Basic Research Project of Yunnan Province(No.2018NS0273)the Medical Reserve Talents Training Program of Yunnan Provincial Health Commission(No.H-2018021)the Yunnan Talent Support Plan-Young Talent Program(No.XDYCQNRC-2022-0702).
文摘Dear Editor,We are writing to present a case of bilateral sequential cytomegalovirus retinitis(CMVR)in a patient with dyskeratosis congenita(DC).DC is an inherited bone marrow failure syndrome characterized by a typical diagnostic triad of oral leukoplakia,nail dystrophy,and reticular hyperpigmentation[1].DC can be inherited in one of the three forms,X-linked,autosomal dominant,and autosomal recessive.
文摘Retinitis pigmentosa(RP)is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium(RPE)cells.Its main clinical manifestations include night blindness and progressive loss of peripheral vision,making it a prevalent debilitating eye disease that significantly impacts patients’quality of life.RP exhibits significant phenotypic and genetic heterogeneity.For instance,numerous abnormal genes are implicated in RP,resulting in varying clinical presentations,disease progression rates,and pathological characteristics among different patients.Consequently,gene therapy for RP poses challenges due to these complexities.However,stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem cells.In recent years,a large number of animal experiments and clinical trials based on stem cell transplantation attempts,especially cord blood mesenchymal stem cell(MSC)transplantation and bone marrow-derived MSC transplantation,have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected eye.However,stem cell therapy also has certain limitations,such as the fact that RP patients may involve multiple types of retinal cytopathia,which brings great challenges to stem cell transplantation therapy,and further research is needed to solve various problems faced by this approach in the clinic.Through comprehensive analysis of the etiology and histopathological changes associated with RP,this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials,while also highlighting the existing limitations that warrant further investigation.
文摘Aim: To report a familial case of syndromic retinitis pigmentosa identified at Aristide Le Dantec Hospital in Dakar and to describe their clinical characteristics ophthalmic. Observation: We report a sibling group of nine children, four died at a young age from unknown causes. Three children were affected by retinitis pigmentosa, two cases were syndromic. A history of nyctalopia was found in all three affected children. The mean age of onset of decreased visual acuity was 6.6 years. Patient 1 affected by syndromic retinitis pigmentosa had an extraocular sign of cystic dilation of the main bile duct. Patient 2 had myoclonic epilepsy, psychomotor retardation, and the molar tooth sign on cerebral MRI (highly suggestive of Joubert syndrome). The third child had isolated retinitis pigmentosa. Ophthalmological examinations (fundus examination, electroretinogram, and visual evoked potentials) and pediatric examinations in the remaining two children were normal. Discussion and Conclusion: Retinitis pigmentosa is a rare degenerative disease that can be associated with several other malformations, highlighting the importance of screening for associated conditions. It presents a grim functional prognosis and a life prognosis dependent on extraocular manifestations. Molecular biology (karyotyping, next-generation sequencing) could have identified the implicated genes and allowed for a formal diagnosis and genetic counseling.
基金Supported by the National Natural Science Foundation of China(No.81271425,No.81860170)the Natural Science Foundation of Jiangxi Province(No.20181ACG70010).
文摘AIM:To characterize the ophthalmic clinical phenotype of a family with retinitis pigmentosa(RP)and closed-angle glaucoma and to detect pathogenic genes and mutation sites causing RP in this family.METHODS:Ophthalmic clinic performance was examined in detail in 8 enrolled family members.Genomic DNA was extracted from the peripheral blood of 4 family members for whole-exome sequencing(WES)to select potential genetic mutations whose structures were identified by bioinformatics analysis.Then,Sanger sequencing was used in 12 family members and control group members to validate and confirm the disease-causing mutation loci,and we analyzed the genotype-phenotype relationships.RESULTS:The known c.512C>T(p.P171L)mutation in the rhodopsin(RHO)gene was only found in afflicted family members and was confirmed by WES and Sanger sequencing as the pathogenic mutation in this family.In addition to being diagnosed with RP,family member III:4 was found to have bilateral closed-angle glaucoma,high myopia,and concurrent cataracts,and family members II:2 and II:4 had pathological changes of anterior chamber angle narrowing.Family members IV:3 and IV:4 were found to have retinoschisis.CONCLUSION:Glaucoma and related pathological changes,such as retinoschisis,in family members are preliminarily considered RP complications caused by RHO mutation.
基金Supported by National Natural Science Foundation of China(No.31751003)Natural Science Foundation of Zhejiang Province(No.LY20H120009)+1 种基金Health Commission of Zhejiang Province(No.2022KY168)Beijing Bethune Charitable Foundation(No.BJ-GY2021013J).
文摘AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic examinations including best corrected visual acuity,fundus photography,vision field,and pattern-visual evoked potential were performed to identify the disease phenotype of a six-yearold boy from the family(proband).Genomic DNA was extracted from peripheral blood of five available members of the pedigree.Whole-exome sequencing(WES),Sanger sequencing,and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR.Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants.RESULTS:The proband was diagnosed as having retinitis pigmentosa(RP).He had severe symptoms with early onset.A novel splicing mutation,c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing.Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped,leading to the subsequent deletion of 623 correct amino acids(c.529_619del p.Val177Glnfs*16).CONCLUSION:We identify a novel splice donor site mutation causing aberrant splicing of RPGR.Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.
文摘Aim: To establish a useful and objective classification for retinitis pigmentosa (RP) to evaluate the disease severity. Methods: This is a retrospective cross-sectional study. Visual acuity (VA), visual field (VF) width, ellipsoid zone width on optic cohorence tomography (OCT) and multifocal electroretinography (mf ERG) values were obtained from medical records of patients with RP. A scoring criterion was developed wherein each variable was assigned a score from 0 to 5 depending on its distribution. The cumulative score (from 0 to 20) was used to classify disease severity from grade 0 to 5. The scores were correlated with each other and the final grade. Results: Data of 152 eyes of 92 patients who had the results of all tests were reviewed. The mean age was 41.2 years. The mean VA of the patients was 0.13 ± 0.16 Snellen lines. The majority of patients had a VA less than 20/40 (88.6%), a visual field smaller than 20<sup>˚</sup> (78%), and an ellipsoid zone width smaller than 7<sup>˚</sup> (84.4%). The majority of the patients (85.4%) were in advanced stage of the disease (Grade 4 and 5). Conclusions: We present a simple, objective and easy to use disease severity classification for RP which can be used to categorize patients and to evaluate and compare treatment results.
基金Supported by National Natural Science Foundation of China(No.8106008181241124 and81360155)the Research to Prevent Blindness Challenge Grant to the Department of Ophthalmology at the University of Rochester
文摘AIMTo make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology.
基金Supported by National Nature Science Foundation of China (No.81760180)Key Research and Development of Ningxia (No.2017BY086)+1 种基金Nature Science Foundation of Ningxia (No.2019AAC03160)Key Research and Development Program of Ningxia (No.2018BEG03051)。
文摘AIM: To identify mutations with whole exome sequencing(WES) in a Chinese X-linked retinitis pigmentosa(XLRP) family. METHODS: Patients received the comprehensive ophthalmic evaluation. Genomic DNA was extracted from peripheral blood and subjected to Sure Select Human All Exon 6+ UTR exon capture kit. The exons were sequenced as 100 base paired reads on Illumina HiS eq2500 system. Only mutations that resulted in a change in amino acid sequence were selected. A pattern of inheritance of the RP family was aligned to identified causal mutation.RESULTS: We analysed the data of WES information from XLRP family. The analysis revealed a hemizygous large genomic deletion of RPGR c.29113 del was responsible for this XLRP. The gross deletion lead to a frame-shift mutation and generate stop codon at 7 animo acid behind Asp(D10 Afs*7), which would serious truncate RPGR protein. The novel frame-shift mutation was found to segregate with retinitis pigmentosa(RP) phenotype in this family. Bilateral myopia was present on the male patients, but carrier female showed unilateral myopia without RP.CONCLUSION: Our study identifies a novel frame-shift mutation of RPGR in a Chinese family, which would expand the spectrum of RPGR mutations. The geno-phenotypic analysis reveals a correlation between RP and myopia. Although exact mechanism of RP related myopia is still unknown, but the novel frame-shift mutation will give our hit on studying the molecular pathogenesis of RP and myopia.
基金Supported by the 1351 Beijing Chaoyang Talent Training Program(No.CYXX-2017-21)
文摘AIM：To compare the effectiveness between multiple intravitreal injections of ganciclovir alone and combined with foscarnet as initial treatment for patients with newlyonset cytomegalovirus retinitis （CMVR）.METHODS：The retrospective study observed 37 patients（58 eyes） who suffered from CMVR onset between 2013 and 2015. Among them, 35 eyes underwent 4 weekly intravitreal injections of 3.0 mg ganciclovir, and 23 eyes underwent 4 weekly injections of 3.0 mg ganciclovir combined with 2.4 mg foscarnet. Visual acuity, intraocular pressure and viral load of cytomegalovirus （CMV） in aqueous humor measured by real-time polymerase chain reaction were compared before and after each injection.RESULTS：CMV-DNA copies in aqueous humor decreased remarkably in both groups. The average of CMV-DNA copies in patients’ aqueous decreased from 38.3×10~4 copies/mL at baseline to 2.2×10~4 copies/mL after the 4^（th） injection in patients who were treated with ganciclovir monotherapy,and decreased from 76.9×10~4 copies/mL to 11.3×10~4 copies/mL after 4 continuous injections of ganciclovir combined with foscarnet. No significant difference was found in reduction of viral load, change of visual acuities or intraocular pressures between monotherapy or combined therapy.CONCLUSION：Results of this study show that the initial effectiveness of treating CMVR after 4 weekly intravitreal injections is not significantly different from ganciclovir alone or combined with foscarnet. Continuous injection of ganciclovir alone is sufficient in treating immunosuppressive patients with newly-onset CMVR.
基金Supported by the National Key Development Program for Basic Research of China (973 research plan, No.2013CB967001)
文摘Retinitis pigmentosa（RP）is a group of heterogeneous inherited retinal diseases that is characterized by primary death rod photoreceptors and the secondary loss of cones.The degeneration of cones causes gradual constriction of visual fields,leaving the central islands that are eventually snuffed out.Studies indicate that the hyperoxia causes oxidative damage in the retina and contributes to the cone death of RP.Moreover,abundant reactive oxidative species（ROS）which are generated in cones may result in mitochondria membrane depolarization,which has been ascribed a central role in the apoptotic process and has been proposed to act as a forward feeding loop for the activation of downstream cascades.Anthocyanin is a potent antioxidant which has been evidenced to be able to counteract oxidative damages,scavenge surplus ROS,and rectify abnormities in the apoptotic cascade.Taken together with its ability to attenuate inflammation which also contributes to the etiology of RP,it is reasonable to hypothesize that the anthocyanin could act as a novel therapeutic strategy to retard or prevent cone degeneration in RP retinas,particularly if the treatment is timed appropriately and delivered efficiently.Future pharmacological investigations will identify the anthocyanin as an effective candidate for PR therapy and refinements of that knowledge would ignite the hope of restoring the visual function in RP patients.
基金Supported by National Natural Science Foundation of China(No.8157089181272981)+2 种基金Beijing Natural Science Foundation(No.7151003)Capital Medical University Fundamental Clinical Research Cooperation Fund(No.16JL73)Beijing Municipal Administration of Hospitals’Ascent Plan(No.DFL20150201)
文摘AIM：To compare the clinical manifestation of cytomegalovirus（CMV）retinitis and microvascular retinopathy（MVR）in patients with acquired immunodeficiency syndrome（AIDS）in China.METHODS：A total of 93 consecutive patients with AIDS,including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed.Highly active antiretroviral therapy（HAART）status was recorded.HIV and CMV immunoassay were also tested.CD4＋T-lymphocyte count and blood CMV-DNA test were performed in all patients.Aqueous humor CMV-DNA test was completed in 39patients.Ophthalmological examinations including best corrected visual acuity（BCVA,by International Standard Vision Chart）,intraocular pressure（IOP）,slit-lamp biomicroscopy,indirect ophthalmoscopy were performed.RESULTS：In MVR group,the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13.Blood CMV-DNA was 0（0,269 000）and 42 patients（80.77%）did not receive HAART.In CMV retinitis group,13 patients（31.71%）had anterior segment abnormality.The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470（0,1 450 000）.Nineteen patients（46.34%）had not received HAART.MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%,respectively.Two patients with MVR progressed to CMV retinitis during the follow-up period.CONCLUSION：In comparison of CMV,patients with MVR have relatively mild visual function impairment.Careful ophthalmological examination and close follow-up are mandatory,especially for patients who have systemic complications,positive CMV-DNA test and without received HAART.
基金Supported by the National Natural Science Foundation of China(No.81360154)
文摘AIM: To detect the pathogenetic mutations responsible for nonsyndromic autosomal recessive retinitis pigmentosa(RP) in 2 nonconsanguineous Chinese families. METHODS: The clinical data, including detailed medical history, best corrected visual acuity(BCVA), slit-lamp biomicroscope examination, fundus photography, optical coherence tomography, static perimetry, and full field electroretinogram, were collected from the members of 2 nonconsanguineous Chinese families preliminarily diagnosed with RP. Genomic DNA was extracted from the probands and other available family members;wholeexome sequencing was conducted with the DNA samples provided by the probands, and all mutations detected by whole-exome sequencing were verified using Sanger sequencing in the probands and the other available family members. The verified novel mutations were further sequenced in 192 ethnicity matched healthy controls.RESULTS: The patients from the 2 families exhibited the typical symptoms of RP, including night blindness and progressive constriction of the visual field, and the fundus examinations showed attenuated retinal arterioles, peripheral bone spicule pigment deposits, and waxy optic discs. Whole-exome sequencing revealed a novel nonsense mutation in FAM161 A(c.943 A>T, p.Lys315*) and compound heterozygous mutations in RP1 L1(c.56 C>A, p.Pro19 His;c.5470 C>T, p.Gln1824*). The nonsense c.5470 C>T, p.Gln1824* mutation was novel. All mutations were verified by Sanger sequencing. The mutation p.Lys315* in FAM161A co-segregated with the phenotype, and all the nonsense mutations were absent from the ethnicity matched healthy controls and all available databases.CONCLUSION: We identify 2 novel mutations in genes responsible for autosomal recessive RP, and the mutation in FAM161A is reported for the first time in a Chinese population. Our result not only enriches the knowledge of the mutation frequency and spectrum in the genes responsible for nonsyndromic RP but also provides a new target for future gene therapy.
基金The work was supported by the National Natural Science Foundation of China,Nos.81470656(to YX),82071372(to AL),82074169(to XSM)Guangdong Grant Key Technologies for Treatment of Brain Disorders’,China,No.2018B030332001(to YX)+3 种基金Ningxia Key Research and Development Program Grant(Yinchuan,Ningxia Hui Autonomous Region,China)(to KFS)Program of Introducing Talents of Discipline to Universities,China,No.B14036(to YX,AL,KFS)Outstanding Scholar Program of Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),No.2018GZR110102002(to KFS,AL)Science and Technology Program of Guangzhou,No.202007030012(to KFS and AL).
文摘Luteolin is neuroprotective for retinal ganglion cells and retinal pigment epithelial cells after oxidative injury,whereby it can inhibit microglial neurotoxicity.Therefore,luteolin holds the potential to be useful for treatment of retinal diseases.The purpose of this study was to investigate whether luteolin exhibits neuroprotective effects on rod cells in rd10 mice,a slow photoreceptor-degenerative model of retinitis pigmentosa.Luteolin(100 mg/kg)intraperitoneally injected daily from postnatal day 14(P14)to P25 significantly enhanced the visual performance and retinal light responses of rd10 mice at P25.Moreover,it increased the survival of photoreceptors and improved retinal structure.Mechanistically,luteolin treatment attenuated increases in reactive oxygen species,photoreceptor apoptosis,and reactive gliosis;increased mRNA levels of anti-inflammatory cytokines while lowering that of pro-inflammatory and chemoattractant cytokines;and lowered the ratio of phospho-JNK/JNK.Application of the JNK inhibitor SP600125 exerted a similar protective effect to luteolin,suggesting that luteolin delays photoreceptor degeneration and functional deterioration in rd10 mice through regulation of retinal oxidation and inflammation by inhibiting the JNK pathway.Therefore,luteolin may be useful as a supplementary treatment for retinitis pigmentosa.This study was approved by the Qualified Ethics Committee of Jinan University,China(approval No.IACUC-20181217-02)on December 17,2018.
基金Supported by the Open Research Project of Key Laboratory of Capital Medical University (No.2017YKSJ04)Capital Medical University Fundamental Clinical Research Cooperation Fund (No.16JL73)
文摘The effect of intravitreal ganciclovir injection combined with intravenous infusion on acquired immune deficiency syndrome(AIDS) patients with cytomegalovirus retinitis(CMVR) was investigated. A total of 32 eyes in 23 AIDS patients diagnosed as CMVR from 2017 to 2018 were included in the retrospective study. All patients underwent induction therapy by using intravenous drip of the anticytomegalovirus(CMV) agent ganciclovir(5 mg/kg q12 h) combined with intravitreal ganciclovir injection(3 mg/time, 2 times/wk). The visual acuity, fundus photographs, lesion location, and number of intravitreal injections were observed preoperatively and postoperatively. Totally 14 eyes were cured during induction therapy. The number of injections [4.13(2 to 6)] in CMVR patients with peripherally fundus lesions were significantly lower than those with central lesions (4.89(2 to 6))The individualized therapy of intravitreal ganciclovir injections for AIDS patients with CMVR can effectively reduce the numbers of intravitreal injections.
文摘Objective To evaluate the prevalence of rhodopsin (RHO) mutations and the genotype-phenotype relationships in Chinese patients with autosomal dominant retinitis pigmentosa (ADRP) by conformation sensitive gel electrophoresis (CSGE) and direct DNA sequencing. Methods We have screened the five coding exons and splice sites of RHO gene in 27 probands who had no relativity from Chinese ADRP families and 100 normal controls to identify disease-associated mutations, using CSGE and direct DNA sequencing. Family members of some probands with disease-associated mutations were also genotyped to determine whether the RHO mutations segregated with retinitis pigmentosa (RP) in their families. Results Two RHO mutations, Pro347Leu and Pro327 (1-bp del), were identified separately in two families, thus the frequency of RHO mutations among this set of Chinese ADRP families is about 7.4% (2/27). Pro347Leu mutation was found in one ADRP proband as well as three her children who also had RP. She had relatively early onset at about 17 years. The only one child without this mutation had no symptom or sign of RP at age of 34. Pro327 (1-bp del) was identified in a late-onset ADRP patient, who appeared night blindness around 30 years old and in her fifties electroretinogram (ERG) has been flat in both scotopic and photopic phases. Family analysis showed that this mutation also existed in her younger dau-ghter and her elder sister, both of them also had RP. Three other family members were genotypically and phenotypically normal. Neither of the two mutations was detected in 100 normal controls.Conclusions The frequency of RHO mutations in Chinese patients was lower than that in Europe and North America. The phenotype of the patients with Pro347Leu corresponded to type 1 ADRP, with severe rod degeneration and some cone preservation later, while the phenotype of the patients carrying Pro327 (1-bp del) corresponded to type 2 ADRP, with a concomitant loss of rod and cone visual function. CSGE was found to be a sensitive, simple, and practical method for the screening of a large number of samples under highly reproducible conditions, and could be utilized in routine molecular diagnostic laboratories.
基金supported by Aier Eye Hospital Group,Nos.AF2019001 and AF2019002(to SBT,KFS,YX and XSM)the National Natural Science Foundation of China,No.82074169(to XSM)+3 种基金Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology of China,No.20200730009(to YX)Guangdong Grant Key Technologies for Treatment of Brain Disorders,China,No.2018B030332001(to YX)Natural Science Foundation of Guangdong Province of China,No.2021A1515012473(to XSM)Project of Administration of Traditional Chinese Medicine of Guangdong Province,No.20202045(to XSM)。
文摘Retinitis pigmentosa is a retinal disease characterized by photoreceptor degeneration.There is currently no effective treatment for retinitis pigmentosa.Although a mixture of lutein and other antioxidant agents has shown promising effects in protecting the retina from degeneration,the role of lutein alone remains unclear.In this study,we administered intragastric lutein to Pde6brd10 model mice,which display degeneration of retinal photoreceptors,on postnatal days 17(P17)to P25,when rod apoptosis reaches peak.Lutein at the optimal protective dose of 200 mg/kg promoted the survival of photoreceptors compared with vehicle control.Lutein increased rhodopsin expression in rod cells and opsin expression in cone cells,in line with an increased survival rate of photoreceptors.Functionally,lutein improved visual behavior,visual acuity,and retinal electroretinogram responses in Pde6brd10 mice.Mechanistically,lutein reduced the expression of glial fibrillary acidic protein in Müller glial cells.The results of this study confirm the ability of lutein to postpone photoreceptor degeneration by reducing reactive gliosis of Müller cells in the retina and exerting anti-inflammatory effects.This study was approved by the Laboratory Animal Ethics Committee of Jinan University(approval No.LACUC-20181217-02)on December 17,2018.
文摘AIM:To investigate the efficacy and the safety of umbilical cord derived mesenchymal stem cell(UC-MSC)implantation in patients with retinitis pigmentosa(RP).METHODS:This prospective,single-center,phase 3 clinical study enrolled 124 eyes of 82 RP patients.The patients received 5 million UC-MSCs to the suprachoroidal area with a surgical procedure.Patients were evaluated on the 1st day,1st,and 6th months postoperatively.Best corrected visual acuity(BCVA),anterior segment and fundus examinations,color photography,optical coherence tomography(OCT),and visual field(VF)tests were carried out at each visit.Fundus fluorescein angiography(FFA)and multifocal electroretinography(mfERG)recordings were performed at the end of the 6th month.Ocular and systemic adverse events of the surgical procedure were also noted.RESULTS:All of the 82 patients completed the 6-month follow-up period.None of them had any serious systemic or ocular complications.There were statistically significant improvements in BCVA and VF during the study(all P<0.05).The amplitudes of the P1 waves in the central areas showed significant improvements in mfERG recordings.There were also significant increases in implicit times of P1 waves in the central areas.CONCLUSION:Suprachoroidal administration of UC-MSCs has beneficial effect on BCVA,VF,and mfERG measurements during the 6-month follow-up period.Cell mediated therapy based on the secretion of growth factors(GFs)seems to be an effective and safe option for degenerative retinal diseases.
基金National Natural Science Foundation of China (No.81973912)Capital’s Funds for Health Improvement and Research (No.CFH2020-2-4183)the State Administration of Traditional Chinese Medicine of the People’s Republic of China (No.0610-2040NF020931)。
文摘Retinitis pigmentosa(RP) is a commonly inherited disease of the retina, which is characterized by progressive loss of visual function due to specific genetic mutations. There are many risk factors that may have effect on the progression of RP, such as inheritance patterns, genotype, gender, age, smoking, physical activity, and other demographic and environmental factors. Baseline visual field conditions, changes of ellipsoid zone, photoreceptor layer thickness, and choroidal structure are reported to be the phenotype risk factors for RP progression. Moreover, aqueous flare and high-sensitivity C-reactive protein are probable inflammation biomarkers for assessing the progression of RP. Increased oxidative stress is considered to be one of the potential factors for the existence of RP. The risk factors can be combined to form a corresponding prediction model to predict disease progression. This review is to summarize the current literature that studies the genetic, environmental, phenotypic, demographic, inflammatory and other risk factors of RP progression and discuss the most reliable risk factors that could provide predictive models.
