Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photo...Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide(Lb GP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of Lb GP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of Lb GP as a protective pre-treatment on days 1–7;intraperitoneal administration of 40 mg/kg N-methylN-nitrosourea to induce photoreceptor injury on day 7;and continuation of orally administered Lb GP on days 8–14. Treatment with Lb GP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. Lb GP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, Lb GP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.展开更多
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
AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY...AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY-09,AST successively and divided into 5 groups,including the control,NaIO_(3),NaIO_(3)+CY-09,NaIO_(3)+AST,and NaIO_(3)+CY-09+AST groups.Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry,enzyme linked immunosorbent assay(ELISA),and Western blotting.Retinal pigment epithelium cell line(ARPE-19 cells)and mouse photoreceptor cells line(661W cells)were also treated with NaIO_(3),CY-09,and AST successively.Cell proliferation was assessed by cell counting kit-8(CCK-8)assay.Apoptosis was analyzed by flow cytometry.Changes in autophagosome morphology were observed by transmission electron microscopy.Quantitative polymerase chain reaction(qPCR)was used to detect NLRP3 and caspase-1.NLRP3,caspase-1,cleaved caspase-1,p62,Beclin-1,and LC3 protein levels were measured by Western blotting.IL-1βand IL-18 were measured by ELISA.RESULTS:Compared with the control group,the activity of NaIO_(3)-treated 661W cells decreased within 24 and 48h,apoptosis increased,NLRP3,caspase-1,IL-1βand IL-18 levels increased,and autophagy-related protein levels increased(P<0.05).Compared with NaIO_(3) group,CY-09 and AST inhibited apoptosis(P<0.05),reduced NLRP3,caspase-1,IL-1βand IL-18 expression(P<0.05),and inhibited autophagy.Compared with the other groups,CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62,Beclin-1,and LC3 in vitro and in vivo(P<0.05).CONCLUSION:CY-09 and AST inhibit NaIO_(3)-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in vivo.CY-09 and AST may protect retina from inflammatory injury.展开更多
The majority of inherited retinal degenerative diseases and dry age-related macular degeneration are characterized by decay of the outer retina and photoreceptors,which leads to progressive loss of vision.The inner re...The majority of inherited retinal degenerative diseases and dry age-related macular degeneration are characterized by decay of the outer retina and photoreceptors,which leads to progressive loss of vision.The inner retina,including second-and third-order retinal neurons,also shows aberrant structural changes at all stages of degeneration.Müller glia,the major glial cells maintain retinal homeostasis,activating and rearranging immediately in response to photoreceptor stress.These phenomena are collectively known as retinal remodeling and are anatomically well described,but their impact on visual function is less well characterized.Retinal remodeling has traditionally been considered a detrimental chain of events that decreases visual function.However,emerging evidence from functional assays suggests that remodeling could also be a part of a survival mechanism wherein the inner retina responds plastically to outer retinal degeneration.The visual system’s first synapses between the photoreceptors and bipolar cells undergo rewiring and functionally compensate to maintain normal signal output to the brain.Distinct classes of retinal ganglion cells remain even after the massive loss of photoreceptors.Müller glia possess the regenerative potential for retinal recovery and possibly exert adaptive transcriptional changes in response to neuronal loss.These types of homeostatic changes could potentially explain the well-maintained visual function observed in patients with inherited retinal degenerative diseases who display prominent anatomic retinal pathology.This review will focus on our current understanding of retinal neuronal and Müller glial adaptation for the potential preservation of retinal activity during photoreceptor degeneration.Targeting retinal self-compensatory responses could help generate universal strategies to delay sensory disease progression.展开更多
·AIM:To evaluate the functional and structural changes of photoreceptors in patients and asymptomatic carriers with Leber hereditary optic neuropathy(LHON)using fullfield electroretinography(FERG)and optical cohe...·AIM:To evaluate the functional and structural changes of photoreceptors in patients and asymptomatic carriers with Leber hereditary optic neuropathy(LHON)using fullfield electroretinography(FERG)and optical coherence tomography(OCT).·METHODS:Individuals diagnosed with LHON at the Renmin Hospital of Wuhan University and their family members were included in this cross-sectional observational study.The FERG a-wave amplitude of affected patients and asymptomatic carriers was analyzed.The thickness of the outer nuclear layer(ONL),inner and outer segment(IS/OS)and total photoreceptors in the macular fovea and parafovea were measured.·RESULTS:This study included 14 LHON patients(mean age:20.00±9.37y),12 asymptomatic carriers(mean age:39.83±6.48y),and 14 normal subjects(mean age:24.20±1.52y).The FERG results showed that the darkadapted 3.0 electroretinography and light-adapted 3.0 electroretinography a-wave amplitudes of patients and carriers were significantly decreased(P<0.001).The ONL and photoreceptors layers were slightly thicker in patients than in normal subjects(P<0.05),whereas they were thinner in carriers(P<0.05).There were no differences in IS/OS thickness among the groups(P>0.05).·CONCLUSION:Photoreceptors function is significantly impaired in LHON-affected patients and asymptomatic carriers.Meanwhile,photoreceptors morphology is slightly altered,mainly manifesting as a change in ONL thickness.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
Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the world.They comprise various diseases,but retinitis pigmentosa is the most frequently observed.Retinitis pigment...Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the world.They comprise various diseases,but retinitis pigmentosa is the most frequently observed.Retinitis pigmentosa is commonly limited to the eye,where there is progressive photoreceptor degeneration,rods and secondarily cones.The mechanisms of cone and rod degeneration continue to be investigated,since most of the mutations causing retinitis pigmentosa affect rods and thus,the secondary death of cones is an intriguing question but,ultimately,the cause of blindness.Understanding the mechanisms of rod and cone degeneration could help us to develop therapies to stop or,at least,slow down the degeneration process.Secondary cone degeneration has been attributed to the trophic dependence between rods and cones,but microglial cell activation could also have a role.In this review,based on previous work carried out in our laboratory in early stages of photoreceptor degeneration in two animal models of retinitis pigmentosa,we show that microglial cell activation is observed prior to the the initiation of photoreceptor death.We also show that there is an increase of the retinal microglial cell densities and invasion of the outer retinal layers by microglial cells.The inhibition of the microglial cells improves photoreceptor survival and morphology,documenting a role for microglial cells in photoreceptor degeneration.Furthermore,these results indicate that the modulation of microglial cell reactivity can be used to prevent or diminish photoreceptor death in inherited photoreceptor degenerations.展开更多
Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age...Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs.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
AIM： To investigate the retinal photoreceptor differentiation potential of human orbital adipose tissue-derived stem cells （ADSCs） generated by enzyme （EN） and explant （EX） culture methods.METHODS： We investig...AIM： To investigate the retinal photoreceptor differentiation potential of human orbital adipose tissue-derived stem cells （ADSCs） generated by enzyme （EN） and explant （EX） culture methods.METHODS： We investigated potentials of human orbital ADSCs to differentiate into photoreceptors through EN and EX culture methods. EN and EX orbital ADSCs were obtained from the same donor during rehabilitative orbital decompression, and then were subject to a 3-step induction using Noggin, DKK-1, IGF-1 and b-FGF at different time points for 38d. Stem cell, eye-field and photoreceptor-related gene and protein markers were measured by reverse transcription-polymerase chain reaction （RT-PCR） and immunofluorescent （IMF） staining.RESULTS： Both EX and EN orbital ADSCs expressed CD133, a marker of cell differentiation. Moreover, PAX6 and rhodopsin, markers of the retinal progenitor cells, were detected from EX and EN orbital ADSCs. In EX orbital ADSCs, PAX6 mRNA was detected on the 17th day and then the rhodopsin mRNA was detected on the 24th day. In contrast, the EN orbital ADSCs expressed PAX6 and rhodopsin mRNA on the 31st day. EX orbital ADSCs expressed rhodopsin protein on the 24th day, while EN orbital ADSCs expressed rhodopsin protein on the 31st day. CONCLUSION： Orbital ADSCs isolated by direct explants culture show earlier and stronger expressions of markers towards eye field and retinal photoreceptor differentiation than those generated by conventional EN method.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
Direct exposure to intensive visible light can lead to solar retinopathy, including macular injury. The signs and symptoms include central scotoma, metamorphopsia, and decreased vision. However, there have been few st...Direct exposure to intensive visible light can lead to solar retinopathy, including macular injury. The signs and symptoms include central scotoma, metamorphopsia, and decreased vision. However, there have been few studies examining retinal injury due to intensive light stimulation at the cellular level. Neural network arrangements and gene expression patterns in zebrafish photoreceptors are similar to those observed in humans, and photoreceptor injury in zebrafish can induce stem cell-based cellular regeneration. Therefore, the zebrafish retina is considered a useful model for studying photoreceptor injury in humans. In the current study, the central retinal photoreceptors of zebrafish were selectively ablated by stimulation with high-intensity light. Retinal injury, cell proliferation and regeneration of cones and rods were assessed at 1, 3 and 7 days post lesion with immunohistochemistry and in situ hybridization. Additionally, a light/dark box test was used to assess zebrafish behavior. The results revealed that photoreceptors were regenerated by 7 days after the light-induced injury. However, the regenerated cells showed a disrupted arrangement at the lesion site. During the injury-regeneration process, the zebrafish exhibited reduced locomotor capacity, weakened phototaxis and increased movement angular velocity. These behaviors matched the morphological changes of retinal injury and regeneration in a number of ways. This study demonstrates that the zebrafish retina has a robust capacity for regeneration. Visual impairment and stress responses following high-intensity light stimulation appear to contribute to the alteration of behaviors.展开更多
AIM: To investigate the expression of TWIK-related arachidonic acid-stimulated K+ channel(TRAAK) in retinal degeneration mice(rd1) and further evaluate how TRAAK affect photoreceptor cell apoptosis.METHODS: The rd1 mi...AIM: To investigate the expression of TWIK-related arachidonic acid-stimulated K+ channel(TRAAK) in retinal degeneration mice(rd1) and further evaluate how TRAAK affect photoreceptor cell apoptosis.METHODS: The rd1 mice were distributed into blank(no treatment), control(1.4% DMSO, intraperitoneal injection) and riluzole groups(4 mg/kg·d, intraperitoneal injection) from postnatal 7 d to 10, 14 and 18 d;C57 group(no treatment), as age-matched wild-type control. The thickness of the outer nuclear layer(ONL) of retina was detected by paraffin section hematoxylin and eosin staining. The expression of TRAAK and the apoptosis of the ONL cells were detected by immunostaining, Western blotting, and real-time polymerase chain reaction. RESULTS: The channel agonist riluzole activated TRAAK and delayed the apoptosis of photoreceptor cells in ONL layer of rd1 mice. Both at mRNA and protein levels, after riluzole treatment, TRAAK expression was significantly upregulated, when compared with the control and blank group. Then we detected a series of apoptosis related mRNA and protein. The anti-apoptotic factor Bcl-2 downregulated and the pro-apoptotic factors Bax and cleaved-caspase-3 upregulated significantly. CONCLUSION: Riluzole elevates the expression of TRAAK and inhibits the development of apoptosis. Activation of TRAAK may have some potential effects to put off photoreceptor apoptosis.展开更多
AIM To investigate the effect of two ways of lipofuscin production(lipid peroxidation and glycation) on lipofuscin fluorescence characteristics and phototoxicity and to compare them with the properties of natural lipo...AIM To investigate the effect of two ways of lipofuscin production(lipid peroxidation and glycation) on lipofuscin fluorescence characteristics and phototoxicity and to compare them with the properties of natural lipofuscin.METHODS Model lipofuscins were prepared on the basis of bovine photoreceptor outer segments(POS) with bisretinoid A2 E addition. One set of samples was prepared from POS modified by lipid peroxidation,while another set from POS modified by glycation with fructose. Fluorescent properties and kinetics of photoinduced superoxide generation of model lipofuscins and human retinal pigment epithelium(RPE) lipofuscin were compared. The fluorescence spectra of samples were measured at 365 nm excitation wavelength and 380-650 emission wavelength. RESULTS The fluorescence spectra of model lipofuscins are almost the same as the spectrum of natural lipofuscin. Visible light irradiation of both model lipofuscins and natural lipofuscin isolated from RPE cells leads to decrease of a fluorescence maximum at 550 nm and to appearance of a distinct,new maximum at 445-460 nm. The rate of photogeneration of reactive oxygen forms by both model lipofuscins was almost the same and approximately two times less than that of RPE lipofuscin granules.CONCLUSION These data suggest that fluorescent characteristics and phototoxicity of lipofuscin granules depend only to an insignificant degree on the oxidative modification of POS proteins and lipids,and generally are defined by the bisretinoid fluorophores contained in them.展开更多
AIM:To investigate the effects of naringenin eye drops on N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death in rats.METHODS:Photoreceptor cell death was induced by single intraperitoneal injection of MNU(6...AIM:To investigate the effects of naringenin eye drops on N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death in rats.METHODS:Photoreceptor cell death was induced by single intraperitoneal injection of MNU(60 mg/kg)in rats.Both eyes of all animals were instilled with one drop of vehicle,0.5% or 1.0% naringenin eye drops three times per day from 7d before to 17d after MNU injection.Effects of naringenin on MNU-induced photoreceptor cell death were evaluated by electrophysiological and histological analysis.RESULTS:Flash electroretinography (FERG)and oscillatory potentials (OPs) recordings showed that the vehicle control group had remarkable reduction of amplitudes and prolongation of latency times.FERG and OPs responses were significantly reversed in MNUinduced rats treated with 0.5%or 1.0% naringenin eye drops compared with the vehicle control.The retinal morphological results showed that naringenin dosedependently preserved the outer nuclear layer,outer retina and total retina.CONCLUSION:These results indicate that topical treatment with naringenin eye drops prevented retinal neurons from MNU-induced structural and functional damages.展开更多
Human bone marrow stem cell (BMSC) may be directed to differentiate into multiple cell types, including adipocyte, chondrocyte, osteocyte and photoreceptor, among others. At present, little is known about the features...Human bone marrow stem cell (BMSC) may be directed to differentiate into multiple cell types, including adipocyte, chondrocyte, osteocyte and photoreceptor, among others. At present, little is known about the features of the BMSC and the protein control mechanism underlying their differentiation into photoreceptor-like cells. In the present study, BMSCs are induced to differentiate into photoreceptor-like cells in an in vitro model simulating the in vivo microenvironment. Up to 32 proteins are identified and differentially expressed through two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to establish a differential protein database for photoreceptor-like cells from BMSC-induced differentiation. Western blot analysis further confirms the expression of some of the identified proteins. The present study proposes the total protein expression and possible molecular mechanism during the differentiation of BMSCs into photoreceptor cells.展开更多
Glycolysis produces large amounts of adenosine triphosphate(ATP)in a short time.The retinal vascular endothelium feeds itself primarily through aerobic glycolysis with less ATP.But when it generates new vessels,aerobi...Glycolysis produces large amounts of adenosine triphosphate(ATP)in a short time.The retinal vascular endothelium feeds itself primarily through aerobic glycolysis with less ATP.But when it generates new vessels,aerobic glycolysis provides rapid and abundant ATP support for angiogenesis,and thus inhibition of glycolysis in endothelial cells can be a target for the treatment of neovascularization.Aerobic glycolysis has a protective effect on Müller cells,and it can provide with a target for visual protection and maintenance of the blood-retinal barrier.Under physiological conditions,the mitochondria of RPE can use lactic acid produced by photoreceptor cells as an energy source to provide ATP for survival.In pathological conditions,because RPE cells avoid their oxidative damage by increasing glycolysis,a large number of glycolysis products accumulate,which in turn has a toxic effect on photoreceptor cells.This shows that stabilizing the function of RPE mitochondria may become a target for the treatment of diseases such as retinal degeneration.The decrease of aerobic glycolysis leads to the decline of photoreceptor cell function and impaired vision;therefore,aerobic glycolysis of stable photoreceptor cells provides a reliable target for delaying vision loss.It is of great significance to study the role of glycolysis in various retinal cells for the targeted treatment of ocular fundus diseases.展开更多
The characteristics of optical waveguide of human photoreceptors play important roles in vision. The mode-field-diameter (MFD) is a very important parameter of a single-mode waveguide, and it is related to many import...The characteristics of optical waveguide of human photoreceptors play important roles in vision. The mode-field-diameter (MFD) is a very important parameter of a single-mode waveguide, and it is related to many important optical characteristics of a single-mode waveguide. Here we show that MFDs of outer segments of human foveal cones are close to the minimum values at their geometric diameter for outer segments of foveal cones. Small MFD of outer segment is important for eyes to have high spatial resolution and low interaction between neighboring cones. We propose that the ellipsoids of foveal cones act as spot size converters to reduce the coupling losses between myoids and outer segments.展开更多
To properly explore the photoreceptor for the negative phototropism in rice （Oryza sativa L.） root, lights with different wavelengths were applied to investigate the effect of light quality on phototropic bending. T...To properly explore the photoreceptor for the negative phototropism in rice （Oryza sativa L.） root, lights with different wavelengths were applied to investigate the effect of light quality on phototropic bending. The phototropic bending could be induced prominently by blue/ultraviolet light, whereas not by red or far-red light. The absorption spectrum of the extracted solution from rice root cap had two peaks at 350 nm and 450 nm, respectively, and the molecular weight of the 120 kD protein in the root cap under unilateral light was larger than that under the dark. It suggested that the blue light receptor might be the photoreceptor for the negative phototropism in rice root.展开更多
Inherited photoreceptor degeneration（IPD）：The human retina is a highly specialised tissue that enables the perception of light across a range of intensities and colours.It covers about65%of the inner surface of the...Inherited photoreceptor degeneration（IPD）：The human retina is a highly specialised tissue that enables the perception of light across a range of intensities and colours.It covers about65%of the inner surface of the eye and contains three layers of cells：the outer nuclear layer（ONL）containing the cell bodies and nuclei of the light-sensitive rod and cone photoreceptorswhose photopigment-containing outer segments form the photoreceptor layer; the inner nuclear layer （INL） containing bipolar, horizontal and amacrine cells; and the ganglion cell layer （GCL） from which the optic nerve arises. There are two layers of synaptic connections between these three layers： the photoreceptors synapse with second order neurons, mainly bi- polar cells, in the outer plexiform layer （OPL）, while in turn the bipolar cells form connections in the inner plexiform layer （IPL） with ganglion cells. The retinal pigment epithelium （RPE） lies directly behind the photoreceptor layer, is heavily pigmented to reduce scattering of light, and is essential for the nourishment, maintenance and metabolism of photoreceptors.展开更多
基金supported by Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology,No.20200730009 (to YX)the National Natural Science Foundation of China,No.82074169 (to XM)+2 种基金the Guangdong Basic and Applied Basic Research Foundation,No.2021A1515012473 (to XM)Project of Administration of Traditional Chinese Medicine of Guangdong Province,No.20202045 (to XM)Aier Eye Hospital Group,No.AF2019001 (to ST,KFS,YX,XM)。
文摘Photoreceptor cell degeneration leads to blindness, for which there is currently no effective treatment. Our previous studies have shown that Lycium barbarum(L. barbarum) polysaccharide(LBP) protects degenerated photoreceptors in rd1, a transgenic mouse model of retinitis pigmentosa. L. barbarum glycopeptide(Lb GP) is an immunoreactive glycoprotein extracted from LBP. In this study, we investigated the potential protective effect of Lb GP on a chemically induced photoreceptor-degenerative mouse model. Wild-type mice received the following: oral administration of Lb GP as a protective pre-treatment on days 1–7;intraperitoneal administration of 40 mg/kg N-methylN-nitrosourea to induce photoreceptor injury on day 7;and continuation of orally administered Lb GP on days 8–14. Treatment with Lb GP increased photoreceptor survival and improved the structure of photoreceptors, retinal photoresponse, and visual behaviors of mice with photoreceptor degeneration. Lb GP was also found to partially inhibit the activation of microglia in N-methyl-N-nitrosourea-injured retinas and significantly decreased the expression of two pro-inflammatory cytokines. In conclusion, Lb GP effectively slowed the rate of photoreceptor degeneration in N-methyl-N-nitrosourea-injured mice, possibly through an anti-inflammatory mechanism, and has potential as a candidate drug for the clinical treatment of photoreceptor degeneration.
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 Key R&D Project(No.2018YFC1106103)Project of Sichuan Medical Association(No.S22058).
文摘AIM:To study the effect of the NLRP3/autophagy pathway on the photoreceptor inflammatory response and the protective mechanism of CY-09 and astaxanthin(AST).METHODS:ICR mice were intraperitoneally injected NaIO_(3),CY-09,AST successively and divided into 5 groups,including the control,NaIO_(3),NaIO_(3)+CY-09,NaIO_(3)+AST,and NaIO_(3)+CY-09+AST groups.Spectral domain optical coherence tomography and flash electroretinogram were examined and the retina tissues were harvested for immunohistochemistry,enzyme linked immunosorbent assay(ELISA),and Western blotting.Retinal pigment epithelium cell line(ARPE-19 cells)and mouse photoreceptor cells line(661W cells)were also treated with NaIO_(3),CY-09,and AST successively.Cell proliferation was assessed by cell counting kit-8(CCK-8)assay.Apoptosis was analyzed by flow cytometry.Changes in autophagosome morphology were observed by transmission electron microscopy.Quantitative polymerase chain reaction(qPCR)was used to detect NLRP3 and caspase-1.NLRP3,caspase-1,cleaved caspase-1,p62,Beclin-1,and LC3 protein levels were measured by Western blotting.IL-1βand IL-18 were measured by ELISA.RESULTS:Compared with the control group,the activity of NaIO_(3)-treated 661W cells decreased within 24 and 48h,apoptosis increased,NLRP3,caspase-1,IL-1βand IL-18 levels increased,and autophagy-related protein levels increased(P<0.05).Compared with NaIO_(3) group,CY-09 and AST inhibited apoptosis(P<0.05),reduced NLRP3,caspase-1,IL-1βand IL-18 expression(P<0.05),and inhibited autophagy.Compared with the other groups,CY-09 combined with AST significantly decreased NLRP3 expression and inhibited the expression of the autophagy-related proteins p62,Beclin-1,and LC3 in vitro and in vivo(P<0.05).CONCLUSION:CY-09 and AST inhibit NaIO_(3)-induced inflammatory damage through the NLRP3/autophagy pathway in vitro and in vivo.CY-09 and AST may protect retina from inflammatory injury.
基金supported by NIH R01EY032492Boston Children’s Hospital(OFD/BTREC/CTREC Faculty Career Development Grant 97906,Pilot Grant 92214,and Ophthalmology Foundation 85010)+5 种基金Mass Lions Eye Foundation 87820Blind Children’s Center 89282(to ZF)Academy of Finland grant 346295Finnish Eye and Tissue Bank FoundationRetina Registered Association(Finland)Sokeain Yst?v?t/De Blindas V?nner Registered Association(to HOL)。
文摘The majority of inherited retinal degenerative diseases and dry age-related macular degeneration are characterized by decay of the outer retina and photoreceptors,which leads to progressive loss of vision.The inner retina,including second-and third-order retinal neurons,also shows aberrant structural changes at all stages of degeneration.Müller glia,the major glial cells maintain retinal homeostasis,activating and rearranging immediately in response to photoreceptor stress.These phenomena are collectively known as retinal remodeling and are anatomically well described,but their impact on visual function is less well characterized.Retinal remodeling has traditionally been considered a detrimental chain of events that decreases visual function.However,emerging evidence from functional assays suggests that remodeling could also be a part of a survival mechanism wherein the inner retina responds plastically to outer retinal degeneration.The visual system’s first synapses between the photoreceptors and bipolar cells undergo rewiring and functionally compensate to maintain normal signal output to the brain.Distinct classes of retinal ganglion cells remain even after the massive loss of photoreceptors.Müller glia possess the regenerative potential for retinal recovery and possibly exert adaptive transcriptional changes in response to neuronal loss.These types of homeostatic changes could potentially explain the well-maintained visual function observed in patients with inherited retinal degenerative diseases who display prominent anatomic retinal pathology.This review will focus on our current understanding of retinal neuronal and Müller glial adaptation for the potential preservation of retinal activity during photoreceptor degeneration.Targeting retinal self-compensatory responses could help generate universal strategies to delay sensory disease progression.
基金Supported by the National Natural Science Foundation of China (No.82101115)Wuhan University Independent Innovation Fund Youth Project (No.2042021kf0094)。
文摘·AIM:To evaluate the functional and structural changes of photoreceptors in patients and asymptomatic carriers with Leber hereditary optic neuropathy(LHON)using fullfield electroretinography(FERG)and optical coherence tomography(OCT).·METHODS:Individuals diagnosed with LHON at the Renmin Hospital of Wuhan University and their family members were included in this cross-sectional observational study.The FERG a-wave amplitude of affected patients and asymptomatic carriers was analyzed.The thickness of the outer nuclear layer(ONL),inner and outer segment(IS/OS)and total photoreceptors in the macular fovea and parafovea were measured.·RESULTS:This study included 14 LHON patients(mean age:20.00±9.37y),12 asymptomatic carriers(mean age:39.83±6.48y),and 14 normal subjects(mean age:24.20±1.52y).The FERG results showed that the darkadapted 3.0 electroretinography and light-adapted 3.0 electroretinography a-wave amplitudes of patients and carriers were significantly decreased(P<0.001).The ONL and photoreceptors layers were slightly thicker in patients than in normal subjects(P<0.05),whereas they were thinner in carriers(P<0.05).There were no differences in IS/OS thickness among the groups(P>0.05).·CONCLUSION:Photoreceptors function is significantly impaired in LHON-affected patients and asymptomatic carriers.Meanwhile,photoreceptors morphology is slightly altered,mainly manifesting as a change in ONL thickness.
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 grants from Fundación Séneca,Agencia de Cienciay Tecnología Región de Murcia,No.19881/GERM/15(to MVS)Spanish Ministry of Economy and Competitiveness,Instituto de Salud Carlos Ⅲ,Fondo Europeo de Desarrollo Regional ‘‘Una 30 Manera de Hacer Europa’’,No.SAF2015-67643-P(to MVS),PI16/00380(to MPVP),RD16/0008/0026(to MPVP),PI16/00031(to MAB)
文摘Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the world.They comprise various diseases,but retinitis pigmentosa is the most frequently observed.Retinitis pigmentosa is commonly limited to the eye,where there is progressive photoreceptor degeneration,rods and secondarily cones.The mechanisms of cone and rod degeneration continue to be investigated,since most of the mutations causing retinitis pigmentosa affect rods and thus,the secondary death of cones is an intriguing question but,ultimately,the cause of blindness.Understanding the mechanisms of rod and cone degeneration could help us to develop therapies to stop or,at least,slow down the degeneration process.Secondary cone degeneration has been attributed to the trophic dependence between rods and cones,but microglial cell activation could also have a role.In this review,based on previous work carried out in our laboratory in early stages of photoreceptor degeneration in two animal models of retinitis pigmentosa,we show that microglial cell activation is observed prior to the the initiation of photoreceptor death.We also show that there is an increase of the retinal microglial cell densities and invasion of the outer retinal layers by microglial cells.The inhibition of the microglial cells improves photoreceptor survival and morphology,documenting a role for microglial cells in photoreceptor degeneration.Furthermore,these results indicate that the modulation of microglial cell reactivity can be used to prevent or diminish photoreceptor death in inherited photoreceptor degenerations.
基金supported by Fundación Carolina,Madrid,SpainFondo Europeo de Desarrollo Regional,Fondo Social Europeo and Consejería de Educación(Grant VA077P17),Junta de Castilla y León,SpainCentro en Red de Medicina Regenerativa y Terapia Celular,Junta de Castilla y León,Spain,respectively
文摘Retinal degenerations are the leading causes of irreversible visual loss worldwide. Many pathologies included under this umbrella involve progressive degeneration and ultimate loss of the photoreceptor cells, with age-related macular degeneration and inherited and ischemic retinal diseases the most relevant. These diseases greatly impact patients' daily lives, with accompanying marked social and economic consequences. However, the currently available treatments only delay the onset or slow progression of visual impairment, and there are no cures for these photoreceptor diseases. Therefore, new therapeutic strategies are being investigated, such as gene therapy, optogenetics, cell replacement, or cell-based neuroprotection. Specifically, stem cells can secrete neurotrophic, immunomodulatory, and anti-angiogenic factors that potentially protect and preserve retinal cells from neurodegeneration. Further, neuroprotection can be used in different types of retinal degenerative diseases and at different disease stages, unlike other potential therapies. This review summarizes stem cell-based paracrine neuroprotective strategies for photoreceptor degeneration, which are under study in clinical trials, and the latest preclinical studies. Effective retinal neuroprotection could be the next frontier in photoreceptor diseases, and the development of novel neuroprotective strategies will address the unmet therapeutic needs.
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.
文摘AIM： To investigate the retinal photoreceptor differentiation potential of human orbital adipose tissue-derived stem cells （ADSCs） generated by enzyme （EN） and explant （EX） culture methods.METHODS： We investigated potentials of human orbital ADSCs to differentiate into photoreceptors through EN and EX culture methods. EN and EX orbital ADSCs were obtained from the same donor during rehabilitative orbital decompression, and then were subject to a 3-step induction using Noggin, DKK-1, IGF-1 and b-FGF at different time points for 38d. Stem cell, eye-field and photoreceptor-related gene and protein markers were measured by reverse transcription-polymerase chain reaction （RT-PCR） and immunofluorescent （IMF） staining.RESULTS： Both EX and EN orbital ADSCs expressed CD133, a marker of cell differentiation. Moreover, PAX6 and rhodopsin, markers of the retinal progenitor cells, were detected from EX and EN orbital ADSCs. In EX orbital ADSCs, PAX6 mRNA was detected on the 17th day and then the rhodopsin mRNA was detected on the 24th day. In contrast, the EN orbital ADSCs expressed PAX6 and rhodopsin mRNA on the 31st day. EX orbital ADSCs expressed rhodopsin protein on the 24th day, while EN orbital ADSCs expressed rhodopsin protein on the 31st day. CONCLUSION： Orbital ADSCs isolated by direct explants culture show earlier and stronger expressions of markers towards eye field and retinal photoreceptor differentiation than those generated by conventional EN method.
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.
基金supported by the National Natural Science Foundation of China,No.81301080,81671179the Fundamental Research Funds for the Central Universities in China,No.63161215the Natural Science Foundation of Tianjin of China,No.15JCYBJC24400,15JCQNJC10900
文摘Direct exposure to intensive visible light can lead to solar retinopathy, including macular injury. The signs and symptoms include central scotoma, metamorphopsia, and decreased vision. However, there have been few studies examining retinal injury due to intensive light stimulation at the cellular level. Neural network arrangements and gene expression patterns in zebrafish photoreceptors are similar to those observed in humans, and photoreceptor injury in zebrafish can induce stem cell-based cellular regeneration. Therefore, the zebrafish retina is considered a useful model for studying photoreceptor injury in humans. In the current study, the central retinal photoreceptors of zebrafish were selectively ablated by stimulation with high-intensity light. Retinal injury, cell proliferation and regeneration of cones and rods were assessed at 1, 3 and 7 days post lesion with immunohistochemistry and in situ hybridization. Additionally, a light/dark box test was used to assess zebrafish behavior. The results revealed that photoreceptors were regenerated by 7 days after the light-induced injury. However, the regenerated cells showed a disrupted arrangement at the lesion site. During the injury-regeneration process, the zebrafish exhibited reduced locomotor capacity, weakened phototaxis and increased movement angular velocity. These behaviors matched the morphological changes of retinal injury and regeneration in a number of ways. This study demonstrates that the zebrafish retina has a robust capacity for regeneration. Visual impairment and stress responses following high-intensity light stimulation appear to contribute to the alteration of behaviors.
基金Supported by National Natural Science Foundation of China (No.81271012)
文摘AIM: To investigate the expression of TWIK-related arachidonic acid-stimulated K+ channel(TRAAK) in retinal degeneration mice(rd1) and further evaluate how TRAAK affect photoreceptor cell apoptosis.METHODS: The rd1 mice were distributed into blank(no treatment), control(1.4% DMSO, intraperitoneal injection) and riluzole groups(4 mg/kg·d, intraperitoneal injection) from postnatal 7 d to 10, 14 and 18 d;C57 group(no treatment), as age-matched wild-type control. The thickness of the outer nuclear layer(ONL) of retina was detected by paraffin section hematoxylin and eosin staining. The expression of TRAAK and the apoptosis of the ONL cells were detected by immunostaining, Western blotting, and real-time polymerase chain reaction. RESULTS: The channel agonist riluzole activated TRAAK and delayed the apoptosis of photoreceptor cells in ONL layer of rd1 mice. Both at mRNA and protein levels, after riluzole treatment, TRAAK expression was significantly upregulated, when compared with the control and blank group. Then we detected a series of apoptosis related mRNA and protein. The anti-apoptotic factor Bcl-2 downregulated and the pro-apoptotic factors Bax and cleaved-caspase-3 upregulated significantly. CONCLUSION: Riluzole elevates the expression of TRAAK and inhibits the development of apoptosis. Activation of TRAAK may have some potential effects to put off photoreceptor apoptosis.
基金The Russian Foundation for Basic Research,No.15-29-03831
文摘AIM To investigate the effect of two ways of lipofuscin production(lipid peroxidation and glycation) on lipofuscin fluorescence characteristics and phototoxicity and to compare them with the properties of natural lipofuscin.METHODS Model lipofuscins were prepared on the basis of bovine photoreceptor outer segments(POS) with bisretinoid A2 E addition. One set of samples was prepared from POS modified by lipid peroxidation,while another set from POS modified by glycation with fructose. Fluorescent properties and kinetics of photoinduced superoxide generation of model lipofuscins and human retinal pigment epithelium(RPE) lipofuscin were compared. The fluorescence spectra of samples were measured at 365 nm excitation wavelength and 380-650 emission wavelength. RESULTS The fluorescence spectra of model lipofuscins are almost the same as the spectrum of natural lipofuscin. Visible light irradiation of both model lipofuscins and natural lipofuscin isolated from RPE cells leads to decrease of a fluorescence maximum at 550 nm and to appearance of a distinct,new maximum at 445-460 nm. The rate of photogeneration of reactive oxygen forms by both model lipofuscins was almost the same and approximately two times less than that of RPE lipofuscin granules.CONCLUSION These data suggest that fluorescent characteristics and phototoxicity of lipofuscin granules depend only to an insignificant degree on the oxidative modification of POS proteins and lipids,and generally are defined by the bisretinoid fluorophores contained in them.
基金Supported by Guangdong Provincial Department of Science and Technology Grant(No.2011B031700052)
文摘AIM:To investigate the effects of naringenin eye drops on N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death in rats.METHODS:Photoreceptor cell death was induced by single intraperitoneal injection of MNU(60 mg/kg)in rats.Both eyes of all animals were instilled with one drop of vehicle,0.5% or 1.0% naringenin eye drops three times per day from 7d before to 17d after MNU injection.Effects of naringenin on MNU-induced photoreceptor cell death were evaluated by electrophysiological and histological analysis.RESULTS:Flash electroretinography (FERG)and oscillatory potentials (OPs) recordings showed that the vehicle control group had remarkable reduction of amplitudes and prolongation of latency times.FERG and OPs responses were significantly reversed in MNUinduced rats treated with 0.5%or 1.0% naringenin eye drops compared with the vehicle control.The retinal morphological results showed that naringenin dosedependently preserved the outer nuclear layer,outer retina and total retina.CONCLUSION:These results indicate that topical treatment with naringenin eye drops prevented retinal neurons from MNU-induced structural and functional damages.
基金National Natural Science Foundation of China (No.81070715)Innovative Platform Foundation of Fujian Province,China(No.2010Y2003)
文摘Human bone marrow stem cell (BMSC) may be directed to differentiate into multiple cell types, including adipocyte, chondrocyte, osteocyte and photoreceptor, among others. At present, little is known about the features of the BMSC and the protein control mechanism underlying their differentiation into photoreceptor-like cells. In the present study, BMSCs are induced to differentiate into photoreceptor-like cells in an in vitro model simulating the in vivo microenvironment. Up to 32 proteins are identified and differentially expressed through two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to establish a differential protein database for photoreceptor-like cells from BMSC-induced differentiation. Western blot analysis further confirms the expression of some of the identified proteins. The present study proposes the total protein expression and possible molecular mechanism during the differentiation of BMSCs into photoreceptor cells.
文摘Glycolysis produces large amounts of adenosine triphosphate(ATP)in a short time.The retinal vascular endothelium feeds itself primarily through aerobic glycolysis with less ATP.But when it generates new vessels,aerobic glycolysis provides rapid and abundant ATP support for angiogenesis,and thus inhibition of glycolysis in endothelial cells can be a target for the treatment of neovascularization.Aerobic glycolysis has a protective effect on Müller cells,and it can provide with a target for visual protection and maintenance of the blood-retinal barrier.Under physiological conditions,the mitochondria of RPE can use lactic acid produced by photoreceptor cells as an energy source to provide ATP for survival.In pathological conditions,because RPE cells avoid their oxidative damage by increasing glycolysis,a large number of glycolysis products accumulate,which in turn has a toxic effect on photoreceptor cells.This shows that stabilizing the function of RPE mitochondria may become a target for the treatment of diseases such as retinal degeneration.The decrease of aerobic glycolysis leads to the decline of photoreceptor cell function and impaired vision;therefore,aerobic glycolysis of stable photoreceptor cells provides a reliable target for delaying vision loss.It is of great significance to study the role of glycolysis in various retinal cells for the targeted treatment of ocular fundus diseases.
文摘The characteristics of optical waveguide of human photoreceptors play important roles in vision. The mode-field-diameter (MFD) is a very important parameter of a single-mode waveguide, and it is related to many important optical characteristics of a single-mode waveguide. Here we show that MFDs of outer segments of human foveal cones are close to the minimum values at their geometric diameter for outer segments of foveal cones. Small MFD of outer segment is important for eyes to have high spatial resolution and low interaction between neighboring cones. We propose that the ellipsoids of foveal cones act as spot size converters to reduce the coupling losses between myoids and outer segments.
基金supported by the National Natural Science Foundation of China(Grant No.30270795)the open foundation of the State Key Laboratory of Plant Physiology and Biochemistry(Grant No.2002001)the Creative Plan of the Science and Technology for Graduate Student in Institute of Jiangsu Province(Grant No.200635).
文摘To properly explore the photoreceptor for the negative phototropism in rice （Oryza sativa L.） root, lights with different wavelengths were applied to investigate the effect of light quality on phototropic bending. The phototropic bending could be induced prominently by blue/ultraviolet light, whereas not by red or far-red light. The absorption spectrum of the extracted solution from rice root cap had two peaks at 350 nm and 450 nm, respectively, and the molecular weight of the 120 kD protein in the root cap under unilateral light was larger than that under the dark. It suggested that the blue light receptor might be the photoreceptor for the negative phototropism in rice root.
基金Work in Dr.Shu’s lab was supported by the Rosetrees Trust(No.M160 and M160-F1)the Fight for Sight,the Glasgow Children’s Hospital Charity(No.YRSS/PSG/2014)the Visual Research Trust(No.VR2014)
文摘Inherited photoreceptor degeneration（IPD）：The human retina is a highly specialised tissue that enables the perception of light across a range of intensities and colours.It covers about65%of the inner surface of the eye and contains three layers of cells：the outer nuclear layer（ONL）containing the cell bodies and nuclei of the light-sensitive rod and cone photoreceptorswhose photopigment-containing outer segments form the photoreceptor layer; the inner nuclear layer （INL） containing bipolar, horizontal and amacrine cells; and the ganglion cell layer （GCL） from which the optic nerve arises. There are two layers of synaptic connections between these three layers： the photoreceptors synapse with second order neurons, mainly bi- polar cells, in the outer plexiform layer （OPL）, while in turn the bipolar cells form connections in the inner plexiform layer （IPL） with ganglion cells. The retinal pigment epithelium （RPE） lies directly behind the photoreceptor layer, is heavily pigmented to reduce scattering of light, and is essential for the nourishment, maintenance and metabolism of photoreceptors.
