AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis  

作　　者：Ruiqi Qiu Mingzhu Yang Xiuxiu Jin Jingyang Liu Weiping Wang Xiaoli Zhang Jinfeng Han Bo Lei 

机构地区：[1]Henan Eye Hospital,Henan Provincial People’s Hospital,People’s Hospital of Zhengzhou University,Zhengzhou,Henan Province,China [2]Eye Institute,Henan Academy of Innovations in Medical Science,Zhengzhou,Henan Province,China [3]Branch of National Clinical Research Center for Ocular Disease,Henan Provincial People’s Hospital,Zhengzhou,Henan Province,China [4]Academy of Medical Science,Zhengzhou University,Zhengzhou,Henan Province,China

出　　处：《Neural Regeneration Research》2025年第8期2408-2419,共12页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ);Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ);Science and Technology Department of Henan Province,No.212102310307(to XJ)。

摘　　要：Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pi

关 键 词：APOPTOSIS AAV2-PDE6B ERK1/2 gene therapy PHOTOTRANSDUCTION PROTEOMICS rd10 retinitis pigmentosa 

分 类 号：R774.13[医药卫生—眼科]