Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis.
Leber congenital amaurosis (LCA) is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12) mice, an LCA2 model caused by a mutation in t...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3432120?pdf=render |
| _version_ | 1828919861730869248 |
|---|---|
| author | Qinxiang Zheng Yueping Ren Radouil Tzekov Yuanping Zhang Bo Chen Jiangping Hou Chunhui Zhao Jiali Zhu Ying Zhang Xufeng Dai Shan Ma Jia Li Jijing Pang Jia Qu Wensheng Li |
| author_facet | Qinxiang Zheng Yueping Ren Radouil Tzekov Yuanping Zhang Bo Chen Jiangping Hou Chunhui Zhao Jiali Zhu Ying Zhang Xufeng Dai Shan Ma Jia Li Jijing Pang Jia Qu Wensheng Li |
| author_sort | Qinxiang Zheng |
| collection | DOAJ |
| description | Leber congenital amaurosis (LCA) is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12) mice, an LCA2 model caused by a mutation in the RPE65 gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65) in one eye, while the contralateral eye served as a control. Proteomics were compared between untreated rd12 and normal control retinas on P14 and P21, and among treated and untreated rd12 retinas and control retinas on P42. Gene therapy in rd12 mice restored retinal function in treated eyes, which was demonstrated by electroretinography (ERG). Proteomic analysis successfully identified 39 proteins expressed differently among the 3 groups. The expression of 3 proteins involved in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock protein 70 and peroxiredoxin 6) were investigated further. Immunofluorescence, Western blot and real-time PCR confirmed the quantitative changes in their expression. Furthermore, cell culture studies suggested that peroxiredoxin 6 could act in an antioxidant role in rd12 mice. Our findings support the feasibility of gene therapy in LCA2 patients and support a role for alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic mechanisms involved in LCA2 disease process. |
| first_indexed | 2024-12-13T21:35:00Z |
| format | Article |
| id | doaj.art-46865d8a1dc1435f921b3939c729579a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:35:00Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-46865d8a1dc1435f921b3939c729579a2022-12-21T23:30:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4485510.1371/journal.pone.0044855Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis.Qinxiang ZhengYueping RenRadouil TzekovYuanping ZhangBo ChenJiangping HouChunhui ZhaoJiali ZhuYing ZhangXufeng DaiShan MaJia LiJijing PangJia QuWensheng LiLeber congenital amaurosis (LCA) is one of the most severe forms of inherited retinal degeneration and can be caused by mutations in at least 15 different genes. To clarify the proteomic differences in LCA eyes, a cohort of retinal degeneration 12 (rd12) mice, an LCA2 model caused by a mutation in the RPE65 gene, were injected subretinally with an AAV vector (scAAV5-smCBA-hRPE65) in one eye, while the contralateral eye served as a control. Proteomics were compared between untreated rd12 and normal control retinas on P14 and P21, and among treated and untreated rd12 retinas and control retinas on P42. Gene therapy in rd12 mice restored retinal function in treated eyes, which was demonstrated by electroretinography (ERG). Proteomic analysis successfully identified 39 proteins expressed differently among the 3 groups. The expression of 3 proteins involved in regulation of apoptosis and neuroptotection (alpha A crystallin, heat shock protein 70 and peroxiredoxin 6) were investigated further. Immunofluorescence, Western blot and real-time PCR confirmed the quantitative changes in their expression. Furthermore, cell culture studies suggested that peroxiredoxin 6 could act in an antioxidant role in rd12 mice. Our findings support the feasibility of gene therapy in LCA2 patients and support a role for alpha A crystallin, heat shock protein 70 and peroxiredoxin 6 in the pathogenetic mechanisms involved in LCA2 disease process.http://europepmc.org/articles/PMC3432120?pdf=render |
| spellingShingle | Qinxiang Zheng Yueping Ren Radouil Tzekov Yuanping Zhang Bo Chen Jiangping Hou Chunhui Zhao Jiali Zhu Ying Zhang Xufeng Dai Shan Ma Jia Li Jijing Pang Jia Qu Wensheng Li Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis. PLoS ONE |
| title | Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis. |
| title_full | Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis. |
| title_fullStr | Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis. |
| title_full_unstemmed | Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis. |
| title_short | Differential proteomics and functional research following gene therapy in a mouse model of Leber congenital amaurosis. |
| title_sort | differential proteomics and functional research following gene therapy in a mouse model of leber congenital amaurosis |
| url | http://europepmc.org/articles/PMC3432120?pdf=render |
| work_keys_str_mv | AT qinxiangzheng differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT yuepingren differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT radouiltzekov differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT yuanpingzhang differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT bochen differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT jiangpinghou differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT chunhuizhao differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT jializhu differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT yingzhang differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT xufengdai differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT shanma differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT jiali differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT jijingpang differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT jiaqu differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis AT wenshengli differentialproteomicsandfunctionalresearchfollowinggenetherapyinamousemodeloflebercongenitalamaurosis |