Inhibition of Vascular Endothelial Growth Factor Reduces Photoreceptor Death in Retinal Neovascular Disease via Neurotrophic Modulation in Müller Glia

⁰Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.

Anti-VEGF therapy for proliferative diabetic retinopathy (PDR) increases beneficial neurotrophic factors. This suggests a mechanism for anti-VEGF

Vascular Endothelial Growth Factor (VEGF) is crucial for angiogenesis and neuronal function.
Proliferative Diabetic Retinopathy (PDR) involves complex molecular changes affecting retinal health.
Understanding neurotrophic factor roles is key to PDR treatment.

To investigate vitreous neurotrophic factor levels in PDR patients with and without anti-VEGF therapy.
To explore the source, variation, and impact of these factors in an oxygen-induced retinopathy (OIR) mouse model.
To elucidate the neuroprotective mechanisms of anti-VEGF therapy in PDR.

Enzyme-Linked Immunosorbent Assay (ELISA) to measure vitreous neurotrophic factors (NGF, NT-3, NT-4, BDNF, GDNF, CNTF).
Oxygen-induced retinopathy (OIR) mouse model to simulate retinopathy conditions.
In vitro studies using primary Müller cells and 661W photoreceptor cell lines under hypoxia.
Investigated the effect of anti-VEGF agents and Müller cell-derived VEGF inhibition.

Vitreous levels of NGF, NT-3, NT-4, BDNF, GDNF, and CNTF were significantly higher in PDR patients who received anti-VEGF therapy.
A statistical correlation was found between vitreous VEGF levels and each neurotrophic factor.
Hypoxia induced neurotrophic factors; anti-VEGF treatment further upregulated NGF, NT-3, NT-4, and downregulated BDNF, GDNF, CNTF in the OIR model, particularly in Müller glia.
Inhibition of Müller cell-derived VEGF mimicked these neurotrophic changes under hypoxia.
Co-cultured photoreceptor cells showed changes in neurotrophic receptors, indicating a protective synergistic effect against apoptosis when VEGF was inhibited.

Regulation of Müller cell-derived neurotrophic factors is a potential mechanism for the neuroprotective effects of anti-VEGF therapy in PDR.
Anti-VEGF therapy may exert neuroprotective benefits by modulating neurotrophic factor expression in PDR.
These findings offer new insights into therapeutic strategies for PDR.

Keywords:

Müller glia Neurotrophic factor Photoreceptor Proliferative diabetic retinopathy Vascular endothelial growth factor