AIM:To analyze the changes in scientific output relating to Leber congenital amaurosis(LCA)and forecast the study trends in this field.METHODS:All of the publications in the field of LCA from 2002 to 2022 were collect...AIM:To analyze the changes in scientific output relating to Leber congenital amaurosis(LCA)and forecast the study trends in this field.METHODS:All of the publications in the field of LCA from 2002 to 2022 were collected from Web of Science(WOS)database.We analyzed the quantity(number of publications),quality(citation and H-index)and development trends(relative research interest,RRI)of published LCA research over the last two decades.Moreover,VOSviewer software was applied to define the co-occurrence network of keywords in this field.RESULTS:A total of 2158 publications were ultimately examined.We found that the focus on LCA kept rising and peaked in 2015 and 2018,which is consistent with the development trend of gene therapy.The USA has contributed most to this field with 1162 publications,56674 citations and the highest H-index value(116).The keywords analysis was divided into five clusters to show the hotspots in the field of LCA,namely mechanism-related,genotype-related,local phenotype-related,system phenotype-related,and therapy-related.We also identified gene therapy and antiretinal degeneration therapy as a major focus in recent years.CONCLUSION:Our study illustrates historical research process and future development trends in LCA field.This may help to guide the orientation for further clinical diagnosis,treatment and scientific research.展开更多
AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 20...AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 2015.Firstly,whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found,and then homozygous sites was selected,candidate sites were annotated,and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant（SIFT）,Polyphen-2,Mutation assessor,Condel,and Functional Analysis through Hidden Markov Models（FATHMM）.Furthermore,Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test.Sanger sequencing was used to validate single-nucleotide variations（SNVs）.Expanded verification was performed in the rest patients.RESULTS：Totally 51 LCA families with 53 patients and24 family members were recruited.A total of 104 SNVs（66 LCA-related genes and 15 co-segregated genes）were submitted for expand verification.The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families.Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion,biological adhesion,retinoid metabolic process,and eye development biological adhesion.Additionally,WFS7 and STAU2 had the highest homozygous frequencies.CONCLUSION：LCA is a highly heterogeneous disease.Mutations in KRT12,CVP1A1,WFS1,and STAU2 may be involved in the development of LCA.展开更多
Background:Leber congenital amaurosis(LCA),primarily characterized by retinal degeneration is the most severe form of inherited retinal dystrophy(IRD)responsible for congenital blindness.The presence of phenotypic het...Background:Leber congenital amaurosis(LCA),primarily characterized by retinal degeneration is the most severe form of inherited retinal dystrophy(IRD)responsible for congenital blindness.The presence of phenotypic heterogeneity makes the diagnosis of LCA challenging,especially in the absence of pronounced disease pathognomonic,yet it can be well comprehended by employing molecular diagnosis.Therefore,the present study aimed to reveal the causative mutations in ten LCA patients with variable phenotypes using clinical exome sequencing(CES).Methods:CES was performed in ten unrelated LCA patients.Ophthalmic information and family history of all patients were obtained to make a meaningful interpretation.The clinical exome data was analyzed and prioritized using a bioinformatics pipeline to identify mutations,which was further validated by Sanger sequencing.Segregation analysis was also performed on available family members.Results:CES led to the identification of causative mutations in nine LCA patients.Seven patients harbored a mutation in six LCA candidate genes,including RPE65,LCA5(n=2),CRX,PRPH2,CEP290,and ALMS1,while two patients possess a mutation in IFT80 and RP1,known to cause other diseases.Three novel mutations in LCA5(c.1823del),CRX(c.848del)and CEP290(c.2483G>T)were identified.The current study reports for the first time,a mutation in PRPH2,CEP290,and ALMS1 from the Indian population.Additionally,we observed a novel association of LCA phenotype with IFT80 known to cause Jeune syndrome.Based on the genetic finding,the patient AS09,who harbored a mutation in the RP1 gene,was re-diagnosed with early-onset retinitis pigmentosa.Conclusion:In conclusion,the results underline the importance of CES in clinically diagnosed LCA patients with variable phenotypes.The correlation between mutations in candidate genes and clinical phenotypes,helps to refine the clinical diagnosis.However,molecular evaluation with a larger cohort of LCA patients is needed for better understanding of the mutational spectrum in southern India.展开更多
Background： Leber congenital amaurosis （LCA） is a group of clinically and genetically heterogeneous retinal dystrophy. To date, 22 genes are known to be responsible for LCA, and some specific phenotypic features co...Background： Leber congenital amaurosis （LCA） is a group of clinically and genetically heterogeneous retinal dystrophy. To date, 22 genes are known to be responsible for LCA, and some specific phenotypic features could provide significant prognostic information for a potential genetic etiology. This study is to identify gene variants responsible for LCA in a Chinese family using direct Sanger sequencing, with the help of phenotype-genotype correlations. Methods： A Chinese family with six members including two individuals affected with t.CA was studied. All pa- tients underwent a complete ophthalmic examination. Based on phenotype-genotype correlation, direct Sanger sequencing was performed to identify the candidate gene on all family members and normal controls. Targeted next-generation sequencing was used to exclude other known LCA genes. Results： By Sanger sequencing, we identified two novel missense variants in the retinol dehydrogenase 12 （RDH12） gene： a c. 164C〉A transversion predicting a p.T55K substitution, and a c.535C〉G transversion predicting a p.H179D substitution. The two affected subjects carried both RDH12 variants, while their parents and offspring carried only one of heterozygous variants, showing complete cosegregation of the variants. The compound heterozygous variants were not present in 600 normal controls Besides, the RDH12 variants were confirmed by targeted next-generation sequencing. Conclusions： The RDH12 compound heterozygous variants might be the cause of the LCA family. Our study adds to the molecular spectrum of RDH12-related retinopathy and offers an effective example of the power of phenotype-genotype correlations in molecular diagnosis of LCA.展开更多
Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the...Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium（RPE）derived retinoid isomerohydrolase（RPE65）to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine,porcine and rodent LCA2 models. The recombinant AAV2.h RPE65v2 adenoassociated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively,could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful,it will lead the way to additional gene therapy attempts to cure monogenic,inherited retinopathies.展开更多
Background： Leber congenital anaaurosis （LCA） is a visual disease which is caused by RPE65 mutations and results in retinal degeneration and severe vision loss in early infancy. According to previous researches, mu...Background： Leber congenital anaaurosis （LCA） is a visual disease which is caused by RPE65 mutations and results in retinal degeneration and severe vision loss in early infancy. According to previous researches, mutations of the RPE65 gene account for 16% of all cases of LCA. This study aimed to identify RPE65 gene mutations in Chinese patients with LCA. Methods： We recruited 52 sporadic patients from Peking University Third Hospital in 2016 and applied Sanger sequencing to identil＇y variants among exons responsible for the disease. The genomic DNAs from blood leukocytes of these patients were isolated, and tile entire coding region of the RPE65 gene was amplified by polymerase chain reaction. We then deterrnined the sequence of RPE65 using ABI 3100 Genetic Analyzer. Results： Our study identified that only 1 out of the 52 patients with LCA carried the previously unreported homozygosis missense mutation c1174A〉C （T392P） of the RPE65 gene. However, the mutation was associated with the disease phenotype and not detected in 100 normal controls. Conclusions： Though we identified a novel missense mutation in the RPE65 gene that causes LCA, our result indicates that RPE65 mutations may not play a major role in the LCA patients in China since only 1 out of the 52 patients carried mutation in the RPE65 gene.展开更多
Gene therapy is a potentially effective treatment for retinal degenerative diseases.Clustered regularly interspaced short palindromic repeats（CRISPR）/CRISPR-associated protein 9（Cas9） system has been developed as ...Gene therapy is a potentially effective treatment for retinal degenerative diseases.Clustered regularly interspaced short palindromic repeats（CRISPR）/CRISPR-associated protein 9（Cas9） system has been developed as a new genome-editing tool in ophthalmic studies.Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa（RP） and leber congenital amaurosis（LCA）.It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus（AAV） and induced pluripotent stem cells（i PSCs）.In this review,we highlight the main points of further prospect of using CRISPR/Cas9 in targeting retinal degeneration.We also emphasize the potential applications of this technique in treating retinal degenerative diseases.展开更多
Inherited retinal diseases(IRD)are a leading cause of blindness in the working age population.The advances in ocular genetics,retinal imaging and molecular biology,have conspired to create the ideal environment for es...Inherited retinal diseases(IRD)are a leading cause of blindness in the working age population.The advances in ocular genetics,retinal imaging and molecular biology,have conspired to create the ideal environment for establishing treatments for IRD,with the first approved gene therapy and the commencement of multiple therapy trials.The scope of this review is to familiarize clinicians and scientists with the current landscape of retinal imaging in IRD.Herein we present in a comprehensive and concise manner the imaging findings of:(I)macular dystrophies(MD)[Stargardt disease(ABCA4),X-linked retinoschisis(RS1),Best disease(BEST1),pattern dystrophy(PRPH2),Sorsby fundus dystrophy(TIMP3),and autosomal dominant drusen(EFEMP1)],(II)cone and cone-rod dystrophies(GUCA1A,PRPH2,ABCA4 and RPGR),(III)cone dysfunction syndromes[achromatopsia(CNGA3,CNGB3,PDE6C,PDE6H,GNAT2,ATF6],blue-cone monochromatism(OPN1LW/OPN1MW array),oligocone trichromacy,bradyopsia(RGS9/R9AP)and Bornholm eye disease(OPN1LW/OPN1MW),(IV)Leber congenital amaurosis(GUCY2D,CEP290,CRB1,RDH12,RPE65,TULP1,AIPL1 and NMNAT1),(V)rod-cone dystrophies[retinitis pigmentosa,enhanced S-Cone syndrome(NR2E3),Bietti crystalline corneoretinal dystrophy(CYP4V2)],(VI)rod dysfunction syndromes(congenital stationary night blindness,fundus albipunctatus(RDH5),Oguchi disease(SAG,GRK1),and(VII)chorioretinal dystrophies[choroideremia(CHM),gyrate atrophy(OAT)].展开更多
Inherited retinal degeneration is a major cause of incurable blindness characterized by loss of retinal photoreceptor cells.Inherited retinal degeneration is characterized by high genetic and phenotypic heterogeneity ...Inherited retinal degeneration is a major cause of incurable blindness characterized by loss of retinal photoreceptor cells.Inherited retinal degeneration is characterized by high genetic and phenotypic heterogeneity with several genes mutated in patients affected by these genetic diseases.The high genetic heterogeneity of these diseases hampers the development of effective therapeutic interventions for the cure of a large cohort of patients.Common cell demise mechanisms can be envisioned as targets to treat patients regardless the specific mutation.One of these targets is the increase of intracellular calcium ions,that has been detected in several murine models of inherited retinal degeneration.Recently,neurotrophic factors that favor the efflux of calcium ions to concentrations below toxic levels have been identified as promising molecules that should be evaluated as new treatments for retinal degeneration.Here,we discuss therapeutic options for inherited retinal degeneration and we will focus on neuroprotective approaches,such as the neuroprotective activity of the Pigment epithelium-derived factor.The characterization of specific targets for neuroprotection opens new perspectives together with many questions that require deep analyses to take advantage of this knowledge and develop new therapeutic approaches.We believe that minimizing cell demise by neuroprotection may represent a promising treatment strategy for retinal degeneration.展开更多
基金Supported by the National Natural Science Foundation of China (No.82171076,No.82101159)Science and Technology Commission of Shanghai Municipality (No.20Z11900400)+2 种基金Shanghai Hospital Development Center (No.SHDC2020CR2040B,No.SHDC2020CR5014)Shanghai Collaborative Innovation Center for Translational Medicine (No.TM202115PT)Shanghai Sailing Program (No.22YF1435500).
文摘AIM:To analyze the changes in scientific output relating to Leber congenital amaurosis(LCA)and forecast the study trends in this field.METHODS:All of the publications in the field of LCA from 2002 to 2022 were collected from Web of Science(WOS)database.We analyzed the quantity(number of publications),quality(citation and H-index)and development trends(relative research interest,RRI)of published LCA research over the last two decades.Moreover,VOSviewer software was applied to define the co-occurrence network of keywords in this field.RESULTS:A total of 2158 publications were ultimately examined.We found that the focus on LCA kept rising and peaked in 2015 and 2018,which is consistent with the development trend of gene therapy.The USA has contributed most to this field with 1162 publications,56674 citations and the highest H-index value(116).The keywords analysis was divided into five clusters to show the hotspots in the field of LCA,namely mechanism-related,genotype-related,local phenotype-related,system phenotype-related,and therapy-related.We also identified gene therapy and antiretinal degeneration therapy as a major focus in recent years.CONCLUSION:Our study illustrates historical research process and future development trends in LCA field.This may help to guide the orientation for further clinical diagnosis,treatment and scientific research.
基金Supported by National Natural Science Foundation of China(No.81470642No.81271045)
文摘AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 2015.Firstly,whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found,and then homozygous sites was selected,candidate sites were annotated,and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant（SIFT）,Polyphen-2,Mutation assessor,Condel,and Functional Analysis through Hidden Markov Models（FATHMM）.Furthermore,Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test.Sanger sequencing was used to validate single-nucleotide variations（SNVs）.Expanded verification was performed in the rest patients.RESULTS：Totally 51 LCA families with 53 patients and24 family members were recruited.A total of 104 SNVs（66 LCA-related genes and 15 co-segregated genes）were submitted for expand verification.The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families.Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion,biological adhesion,retinoid metabolic process,and eye development biological adhesion.Additionally,WFS7 and STAU2 had the highest homozygous frequencies.CONCLUSION：LCA is a highly heterogeneous disease.Mutations in KRT12,CVP1A1,WFS1,and STAU2 may be involved in the development of LCA.
基金supported by the Department of Biotechnology under Grant BT/NNT/28/SP18830/2018.
文摘Background:Leber congenital amaurosis(LCA),primarily characterized by retinal degeneration is the most severe form of inherited retinal dystrophy(IRD)responsible for congenital blindness.The presence of phenotypic heterogeneity makes the diagnosis of LCA challenging,especially in the absence of pronounced disease pathognomonic,yet it can be well comprehended by employing molecular diagnosis.Therefore,the present study aimed to reveal the causative mutations in ten LCA patients with variable phenotypes using clinical exome sequencing(CES).Methods:CES was performed in ten unrelated LCA patients.Ophthalmic information and family history of all patients were obtained to make a meaningful interpretation.The clinical exome data was analyzed and prioritized using a bioinformatics pipeline to identify mutations,which was further validated by Sanger sequencing.Segregation analysis was also performed on available family members.Results:CES led to the identification of causative mutations in nine LCA patients.Seven patients harbored a mutation in six LCA candidate genes,including RPE65,LCA5(n=2),CRX,PRPH2,CEP290,and ALMS1,while two patients possess a mutation in IFT80 and RP1,known to cause other diseases.Three novel mutations in LCA5(c.1823del),CRX(c.848del)and CEP290(c.2483G>T)were identified.The current study reports for the first time,a mutation in PRPH2,CEP290,and ALMS1 from the Indian population.Additionally,we observed a novel association of LCA phenotype with IFT80 known to cause Jeune syndrome.Based on the genetic finding,the patient AS09,who harbored a mutation in the RP1 gene,was re-diagnosed with early-onset retinitis pigmentosa.Conclusion:In conclusion,the results underline the importance of CES in clinically diagnosed LCA patients with variable phenotypes.The correlation between mutations in candidate genes and clinical phenotypes,helps to refine the clinical diagnosis.However,molecular evaluation with a larger cohort of LCA patients is needed for better understanding of the mutational spectrum in southern India.
基金supported by the National Natural Science Foundation of China(No.81300741)
文摘Background： Leber congenital amaurosis （LCA） is a group of clinically and genetically heterogeneous retinal dystrophy. To date, 22 genes are known to be responsible for LCA, and some specific phenotypic features could provide significant prognostic information for a potential genetic etiology. This study is to identify gene variants responsible for LCA in a Chinese family using direct Sanger sequencing, with the help of phenotype-genotype correlations. Methods： A Chinese family with six members including two individuals affected with t.CA was studied. All pa- tients underwent a complete ophthalmic examination. Based on phenotype-genotype correlation, direct Sanger sequencing was performed to identify the candidate gene on all family members and normal controls. Targeted next-generation sequencing was used to exclude other known LCA genes. Results： By Sanger sequencing, we identified two novel missense variants in the retinol dehydrogenase 12 （RDH12） gene： a c. 164C〉A transversion predicting a p.T55K substitution, and a c.535C〉G transversion predicting a p.H179D substitution. The two affected subjects carried both RDH12 variants, while their parents and offspring carried only one of heterozygous variants, showing complete cosegregation of the variants. The compound heterozygous variants were not present in 600 normal controls Besides, the RDH12 variants were confirmed by targeted next-generation sequencing. Conclusions： The RDH12 compound heterozygous variants might be the cause of the LCA family. Our study adds to the molecular spectrum of RDH12-related retinopathy and offers an effective example of the power of phenotype-genotype correlations in molecular diagnosis of LCA.
文摘Leber＇s congenital amaurosis（LCA）and recent gene therapy advancement for treating inherited retinopathies were extensive literature reviewed using MEDLINE,Pub Med and EMBASE. Adeno-associated viral vectors were the most utilised vectors for ocular gene therapy. Cone photoreceptor cells might use an alternate pathway which was not reliant of the retinal pigment epithelium（RPE）derived retinoid isomerohydrolase（RPE65）to access the 11-cis retinal dehydechromophore. Research efforts dedicated on the progression of a gene-based therapy for the treatment of LCA2. Such gene therapy approaches were extremely successful in canine,porcine and rodent LCA2 models. The recombinant AAV2.h RPE65v2 adenoassociated vector contained the RPE65 cDNA and was replication deficient. Its in vitro injection in target cells induced RPE65 protein production. The gene therapy trials that were so far conducted for inherited retinopathies have generated promising results. Phase I clinical trials to cure LCA and choroideremia demonstrated that adeno-associated viral vectors containing RPE genes and photoreceptors respectively,could be successfully administered to inherited retinopathy patients. A phase III trial is presently ongoing and if successful,it will lead the way to additional gene therapy attempts to cure monogenic,inherited retinopathies.
基金This study was supported by grants from the Science and Technology Commission of Beijing Municipality Fund Project （No. Z171100000417039） and National Natural Science Foundation of China （No. 81300789）.
文摘Background： Leber congenital anaaurosis （LCA） is a visual disease which is caused by RPE65 mutations and results in retinal degeneration and severe vision loss in early infancy. According to previous researches, mutations of the RPE65 gene account for 16% of all cases of LCA. This study aimed to identify RPE65 gene mutations in Chinese patients with LCA. Methods： We recruited 52 sporadic patients from Peking University Third Hospital in 2016 and applied Sanger sequencing to identil＇y variants among exons responsible for the disease. The genomic DNAs from blood leukocytes of these patients were isolated, and tile entire coding region of the RPE65 gene was amplified by polymerase chain reaction. We then deterrnined the sequence of RPE65 using ABI 3100 Genetic Analyzer. Results： Our study identified that only 1 out of the 52 patients with LCA carried the previously unreported homozygosis missense mutation c1174A〉C （T392P） of the RPE65 gene. However, the mutation was associated with the disease phenotype and not detected in 100 normal controls. Conclusions： Though we identified a novel missense mutation in the RPE65 gene that causes LCA, our result indicates that RPE65 mutations may not play a major role in the LCA patients in China since only 1 out of the 52 patients carried mutation in the RPE65 gene.
文摘Gene therapy is a potentially effective treatment for retinal degenerative diseases.Clustered regularly interspaced short palindromic repeats（CRISPR）/CRISPR-associated protein 9（Cas9） system has been developed as a new genome-editing tool in ophthalmic studies.Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa（RP） and leber congenital amaurosis（LCA）.It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus（AAV） and induced pluripotent stem cells（i PSCs）.In this review,we highlight the main points of further prospect of using CRISPR/Cas9 in targeting retinal degeneration.We also emphasize the potential applications of this technique in treating retinal degenerative diseases.
基金Supported by grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology,Macular Society(UK),Fight for Sight(UK),Onassis Foundation,Leventis Foundation,The Wellcome Trust(099173/Z/12/Z)Moorfields Eye Hospital Special Trustees,Moorfields Eye Charity,Retina UK,and the Foundation Fighting Blindness(USA).
文摘Inherited retinal diseases(IRD)are a leading cause of blindness in the working age population.The advances in ocular genetics,retinal imaging and molecular biology,have conspired to create the ideal environment for establishing treatments for IRD,with the first approved gene therapy and the commencement of multiple therapy trials.The scope of this review is to familiarize clinicians and scientists with the current landscape of retinal imaging in IRD.Herein we present in a comprehensive and concise manner the imaging findings of:(I)macular dystrophies(MD)[Stargardt disease(ABCA4),X-linked retinoschisis(RS1),Best disease(BEST1),pattern dystrophy(PRPH2),Sorsby fundus dystrophy(TIMP3),and autosomal dominant drusen(EFEMP1)],(II)cone and cone-rod dystrophies(GUCA1A,PRPH2,ABCA4 and RPGR),(III)cone dysfunction syndromes[achromatopsia(CNGA3,CNGB3,PDE6C,PDE6H,GNAT2,ATF6],blue-cone monochromatism(OPN1LW/OPN1MW array),oligocone trichromacy,bradyopsia(RGS9/R9AP)and Bornholm eye disease(OPN1LW/OPN1MW),(IV)Leber congenital amaurosis(GUCY2D,CEP290,CRB1,RDH12,RPE65,TULP1,AIPL1 and NMNAT1),(V)rod-cone dystrophies[retinitis pigmentosa,enhanced S-Cone syndrome(NR2E3),Bietti crystalline corneoretinal dystrophy(CYP4V2)],(VI)rod dysfunction syndromes(congenital stationary night blindness,fundus albipunctatus(RDH5),Oguchi disease(SAG,GRK1),and(VII)chorioretinal dystrophies[choroideremia(CHM),gyrate atrophy(OAT)].
基金supported by grants from the Telethon Foundation(GGP14180,GGP19113)the European Union(LSHGCT-2005-512036 and transMed,MSCA-ITN-2017-765441)(all to VM)
文摘Inherited retinal degeneration is a major cause of incurable blindness characterized by loss of retinal photoreceptor cells.Inherited retinal degeneration is characterized by high genetic and phenotypic heterogeneity with several genes mutated in patients affected by these genetic diseases.The high genetic heterogeneity of these diseases hampers the development of effective therapeutic interventions for the cure of a large cohort of patients.Common cell demise mechanisms can be envisioned as targets to treat patients regardless the specific mutation.One of these targets is the increase of intracellular calcium ions,that has been detected in several murine models of inherited retinal degeneration.Recently,neurotrophic factors that favor the efflux of calcium ions to concentrations below toxic levels have been identified as promising molecules that should be evaluated as new treatments for retinal degeneration.Here,we discuss therapeutic options for inherited retinal degeneration and we will focus on neuroprotective approaches,such as the neuroprotective activity of the Pigment epithelium-derived factor.The characterization of specific targets for neuroprotection opens new perspectives together with many questions that require deep analyses to take advantage of this knowledge and develop new therapeutic approaches.We believe that minimizing cell demise by neuroprotection may represent a promising treatment strategy for retinal degeneration.
