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

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外文摘要：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 subretina l ly 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 PDE6β expression,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 phototransduction-related 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 pigmentosa.

外文关键词：

apoptosisAAV2-PDE6BERK1/2gene therapyphototransductionproteomicsrd10retinitis pigmentosa

作者：

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

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作者单位：

Henan Eye Hospital,Henan Provincial People's Hospital,People's Hospital of Zhengzhou University,Zhengzhou,Henan Province,China

Eye Institute,Henan Academy of Innovations in Medical Science,Zhengzhou,Henan Province,China

Branch of National Clinical Research Center for Ocular Disease,Henan Provincial People's Hospital,Zhengzhou,Henan Province,China

Academy of Medical Science,Zhengzhou University,Zhengzhou,Henan Province,China

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-01301

中国神经再生研究(英文版)

中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902

ISSN：1673-5374

年,卷(期)：2025.20(8)