Inefficacy of anti-VEGF therapy reflected in VEGF-mediated photoreceptor degeneration

• Published in: Molecular therapy. Nucleic acids 2024-06, Vol.35 (2), p.102176-102176, Article 102176
• Main Authors: Xu, Xin, Han, Ni, Zhao, Fangkun, Fan, Ruoyue, Guo, Qingguo, Han, Xuefei, Liu, Ying, Luo, Guangzuo
• Format: Article
• Language: English
• Subjects: anti-VEGF monotherapy; gene therapy; MT: Delivery Strategies; Original; oxidative stress; photoreceptor degeneration; retinal neovascularization
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2024.102176

Retinal neovascularization (RNV) is primarily driven by vascular endothelial growth factor (VEGF). However, current anti-VEGF therapies are limited by short half-lives and repeated injections, which reduce patient quality of life and increase medical risks. Additionally, not all patients benefit from anti-VEGF monotherapy, and some problems, such as unsatisfactory vision recovery, persist after long-term treatment. In this study, we constructed a recombinant adeno-associated virus (AAV), AAV2-SPLTH, which encodes an anti-VEGF antibody similar to bevacizumab, and assessed its effects in a doxycycline-induced Tet-opsin-VEGFA mouse model of RNV. AAV2-SPLTH effectively inhibited retinal leakage, RNV progression, and photoreceptor apoptosis in a Tet-opsin-VEGF mouse model. However, proteomic sequencing showed that AAV2-SPLTH failed to rescue the expression of phototransduction-related genes, which corresponded to reduced photoreceptor cell numbers. This study suggests that anti-VEGF monotherapy can significantly inhibit RNV to some extent but may not be enough to save visual function in the long term. [Display omitted] Luo and colleagues constructed AAV2-SPLTH, which encoded an anti-VEGF antibody similar to bevacizumab. The results of this study suggested that anti-VEGF monotherapy can significantly inhibit RNV to some extent but may not be enough to save visual function in the long term.