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

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 fro...

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Main Authors: Xin Xu (Author), Ni Han (Author), Fangkun Zhao (Author), Ruoyue Fan (Author), Qingguo Guo (Author), Xuefei Han (Author), Ying Liu (Author), Guangzuo Luo (Author)
Format: Book
Published: Elsevier, 2024-06-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Xin Xu  |e author 
700 1 0 |a Ni Han  |e author 
700 1 0 |a Fangkun Zhao  |e author 
700 1 0 |a Ruoyue Fan  |e author 
700 1 0 |a Qingguo Guo  |e author 
700 1 0 |a Xuefei Han  |e author 
700 1 0 |a Ying Liu  |e author 
700 1 0 |a Guangzuo Luo  |e author 
245 0 0 |a Inefficacy of anti-VEGF therapy reflected in VEGF-mediated photoreceptor degeneration 
260 |b Elsevier,   |c 2024-06-01T00:00:00Z. 
500 |a 2162-2531 
500 |a 10.1016/j.omtn.2024.102176 
520 |a 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. 
546 |a EN 
690 |a MT: Delivery Strategies 
690 |a anti-VEGF monotherapy 
690 |a gene therapy 
690 |a photoreceptor degeneration 
690 |a oxidative stress 
690 |a retinal neovascularization 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Molecular Therapy: Nucleic Acids, Vol 35, Iss 2, Pp 102176- (2024) 
787 0 |n http://www.sciencedirect.com/science/article/pii/S2162253124000635 
787 0 |n https://doaj.org/toc/2162-2531 
856 4 1 |u https://doaj.org/article/61fa65ed1d6348539fd3acd8f6a1b6d0  |z Connect to this object online.