alu-rna-transfected-primary-mouse-retinal-pigment-epithelium

Alu RNA-transfected Primary Mouse Retinal Pigment Epithelium: A Pathologically Relevant In Vitro Model for Age-related Macular Degeneration

Age-related macular degeneration (AMD), particularly non-exudative AMD, requires experimental models that better replicate human pathology. Current in ...

Shanghai Jiao Tong University School of Medicine

National Clinical Research Center for Eye Diseases

Shanghai Key Laboratory of Ocular Fundus Diseases

Adeno-associated virus (AAV) gene therapy is a promising approach for treating ocular monogenic or acquired diseases, though immunogenicity and safety remain critical considerations. We conducted a systematic review of 120 trials and 32 publications to assess immune responses across different delivery routes. Intravitreal administration was associated with higher rates of anterior uveitis (43.06% vs. 10.22%) and intermediate/posterior uveitis (40.36% vs. 6.18%) compared to subretinal delivery. Engineered AAV capsids, used exclusively in intravitreal studies, showed no significant difference in either type of uveitis incidence compared to natural serotypes. Prophylactic immunosuppression (PI) did not affect ocular or systemic immune responses in subretinal delivery, but significantly reduced systemic immune responses in intravitreal administration. These findings underscore the potential of PI to mitigate systemic immune responses in intravitreal AAV therapy. This review should help guide the choice of routes of administration and immunosuppression strategies, and highlights current trends in ocular AAV gene therapy.

Yuhao Tang

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