Retinal BMI1 Expression Preserves Photoreceptors in Sodium-Iodate-Induced Oxidative Stress Models
Year: 2025
Type: article
Abstract: Dry age-related macular degeneration (AMD) is a leading cause of blindness in people over 50 with limited therapeutic options. The sodium iodate (NaIO3)-induced retinal degeneration model mimics oxidative stress-induced cell death in dry AMD. BMI1, a polycomb ring finger protein involved in DNA repair and cell renewal, is a potential therapeutic target for oxidative retinal injury. We evaluated the efficacy of AAV-mediated BMI1 gene delivery in Balb/c and C57BL/6 mice using two routes: subretinal (SR) and suprachoroidal (SC). AAV5.BMI1 (1×10⁹ vg/eye) was delivered SR in Balb/c mice, and efficacy was assessed after 4 and 15 weeks. AAV8.BMI1 (5×10⁹ or 1×10¹⁰ vg/eye) was administered SC in C57BL/6 mice, with evaluation after 4 weeks. Control groups received BSS or AAV8.stuffer. Following NaIO₃ administration, retinal function and structure were analyzed by optical coherence tomography (OCT), electroretinography (ERG), histology, and tissue assays. SC delivery of AAV8.BMI1 achieved the highest transduction and BMI1 expression without adverse effects, leading to dose-dependent ONL preservation and improved ERG responses. These findings suggest that SC AAV-mediated BMI1 gene delivery effectively enhances retinal health and function and prevents retinal degeneration, supporting its use as a promising therapeutic approach for intermediate AMD to prevent advanced disease.
DOI: 10.3390/ijms26125907
Authors: Zhongyang Lu, Shufeng Liu, Maria Gabriela Morales, Andy Whitlock, Ram Ramkumar, Hema Ramkumar
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4411453864