Ocular cells like,retinal pigment epithelium(RPE)is a highly specialized pigmented monolayer of post-mitotic cells,which is located in the posterior segment of the eye between neuro sensory retina and vascular choroid...Ocular cells like,retinal pigment epithelium(RPE)is a highly specialized pigmented monolayer of post-mitotic cells,which is located in the posterior segment of the eye between neuro sensory retina and vascular choroid.It functions as a selective barrier and nourishes retinal visual cells.As a result of high-level oxygen consumption of retinal cells,RPE cells are vulnerable to chronic oxidative stress and an increased level of reactive oxygen species(ROS)generated from mitochondria.These oxidative stress and ROS generation in retinal cells lead to RPE degeneration.Various sources including mtDNA damage could be an important factor of oxidative stress in RPE.Gene therapy and mitochondrial transfer studies are emerging fields in ocular disease research.For retinal degenerative diseases stem cell-based transplantation methods are developed from basic research to preclinical and clinical trials.Translational research contributions of gene and cell therapy would be a new strategy to prevent,treat and cure various ocular diseases.This review focuses on the effect of oxidative stress in ocular cell degeneration and recent translational researches on retinal degenerative diseases to cure blindness.展开更多
Rett syndrome(RTT)is a rare X-linked brain disorder predominantly in females,caused by mutations in Methyl-CpGBinding Protein2(MECP2)gene with the characteristic features of progressive developmental delay,severe inte...Rett syndrome(RTT)is a rare X-linked brain disorder predominantly in females,caused by mutations in Methyl-CpGBinding Protein2(MECP2)gene with the characteristic features of progressive developmental delay,severe intellectual disability,microcephaly,retarded growth,loss of communication abilities,loss of purposeful hand movements,abnormal walking or gait abnormalities,repetitive hand movements,abnormal breathing,irritability and abnormal behaviours.1 Over the last five years,more than eighty genes related to RTT were found using next generation sequencing.2 Here we presented a comprehensive clinical report of a 38-year-old RTT woman having de novo heterozygous Laminin Subunit Gamma 3 gene(LAMC3)mutation G>A(Chr9:133944387;p.C947Y)links with RTT neurological dysfunctions,brain malformations,reduced brain volume and hypoplasia of corpus callosum.This new finding supports the possibility of targeting LAMC3 gene for rescuing the neuropathology of RTT.Other deleterious mutations found in genes such as,CACNA1B(rs4422842),CUBN(rs2271460),GPATCH3(rs779537923),TUBB1(rs463312),KCNJ5(rs768906222),VWA5A(rs551469534),DNAAF1(rs751148678),and PARP1(rs3219145)were unreported in RTT patients.展开更多
基金The authors would like to thank the Science and Engi・neering Research Board(ECR/2018/000718)Indian Council of Medical Research(File No.2018-2786/CMB/Adhoc-BMS)and Countil for Scie ntific and In dustrial Research((Ref No.:27(0353)/19/EMR-ll),Government of India,New Delhi for providing necessary funding to complete this review article successfully.
文摘Ocular cells like,retinal pigment epithelium(RPE)is a highly specialized pigmented monolayer of post-mitotic cells,which is located in the posterior segment of the eye between neuro sensory retina and vascular choroid.It functions as a selective barrier and nourishes retinal visual cells.As a result of high-level oxygen consumption of retinal cells,RPE cells are vulnerable to chronic oxidative stress and an increased level of reactive oxygen species(ROS)generated from mitochondria.These oxidative stress and ROS generation in retinal cells lead to RPE degeneration.Various sources including mtDNA damage could be an important factor of oxidative stress in RPE.Gene therapy and mitochondrial transfer studies are emerging fields in ocular disease research.For retinal degenerative diseases stem cell-based transplantation methods are developed from basic research to preclinical and clinical trials.Translational research contributions of gene and cell therapy would be a new strategy to prevent,treat and cure various ocular diseases.This review focuses on the effect of oxidative stress in ocular cell degeneration and recent translational researches on retinal degenerative diseases to cure blindness.
基金This study was funded by University Grants Commission e National Fellowship for Scheduled Caste Candidates Mrs.Mohan Gomathi,UGC-RGNF SRF(Award number and date:F1-17.1/2017-18/RGNF-2017-18-SC-TAM-35724/(SA-III/Website)02/08/2017)also this study was supported by grants from the Science and Engineering Research Board Early Career Research(ECR)Award funded by the Government of India,New Delhi(No.ECR/2016/001688)Further this study was also funded by the Advanced State Level Biotech Hub,Mizoram University sponsored by Department of Biotechnology,Govt.of India,New Delhi.
文摘Rett syndrome(RTT)is a rare X-linked brain disorder predominantly in females,caused by mutations in Methyl-CpGBinding Protein2(MECP2)gene with the characteristic features of progressive developmental delay,severe intellectual disability,microcephaly,retarded growth,loss of communication abilities,loss of purposeful hand movements,abnormal walking or gait abnormalities,repetitive hand movements,abnormal breathing,irritability and abnormal behaviours.1 Over the last five years,more than eighty genes related to RTT were found using next generation sequencing.2 Here we presented a comprehensive clinical report of a 38-year-old RTT woman having de novo heterozygous Laminin Subunit Gamma 3 gene(LAMC3)mutation G>A(Chr9:133944387;p.C947Y)links with RTT neurological dysfunctions,brain malformations,reduced brain volume and hypoplasia of corpus callosum.This new finding supports the possibility of targeting LAMC3 gene for rescuing the neuropathology of RTT.Other deleterious mutations found in genes such as,CACNA1B(rs4422842),CUBN(rs2271460),GPATCH3(rs779537923),TUBB1(rs463312),KCNJ5(rs768906222),VWA5A(rs551469534),DNAAF1(rs751148678),and PARP1(rs3219145)were unreported in RTT patients.
