Gene Therapy Activates Retinal Pigment Epithelium Cell Proliferation for Age-related Macular Degeneration in a Mouse Model
摘要Objective:Age-related macular degeneration(AMD)is a degenerative retinal disease.The degeneration or death of retinal pigment epithelium(RPE)cells is implicated in the pathogenesis of AMD.This study aimed to activate the proliferation of RPE cells in vivo by using an adeno-associated virus(AAV)vector encoding β-catenin to treat AMD in a mouse model.Methods:Mice were intravitreally injected with AAV2/8-Y733F-VMD2-β-catenin for 2 or 4 weeks,and β-catenin expression was measured using immunofluorescence staining,real-time quantitative reverse transcription polymerase chain reaction(PCR),and Western blotting.The function of β-catenin was determined using retinal flat mounts and laser-induced damage models.Finally,the safety of AAV2/8-Y733F-VMD2-β-catenin was evaluated by multiple intravitreal injections.Results:AAV2/8-Y733F-VMD2-β-catenin induced the expression of β-catenin in RPE cells.It activated the proliferation of RPE cells and increased cyclin D1 expression.It was beneficial to the recovery of laser-induced damage by activating the proliferation of RPE cells.Furthermore,it could induce apoptosis of RPE cells by increasing the expression of Trp53,Bax and caspase3 while decreasing the expression of Bel-2.Conclusion:AAV2/8-Y733F-VMD2-β-catenin increased β-catenin expression in RPE cells,activated RPE cell proliferation,and helped mice heal from laser-induced eye injury.Furthermore,it could induce the apoptosis of RPE cells.Therefore,it may be a safe approach for AMD treatment.
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