VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Diabetic retinopathy (DR) involves Müller cell (MC) dysfunction.
• Vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) are implicated in retinal health.
• Understanding their interplay in MCs under diabetic conditions is crucial for neuroprotection.

Purpose of the Study:

• To elucidate the roles of VEGF and BDNF in MC viability and neuroprotection in DR.
• To investigate VEGF's effect on MC viability and BDNF production.
• To determine BDNF's impact on MC viability under diabetic stress.

Main Methods:

• Primary mouse MCs and rat rMC1 cells were cultured under diabetic conditions.
• Recombinant VEGF (rVEGF) and BDNF (rBDNF) treatments were applied.
• VEGF-stimulated BDNF production was confirmed in vivo.
• BDNF receptor tropomyosin receptor kinase B (TRK-B) was targeted using siRNA knockdown.
• Levels of phosphorylated AKT and ERK were assessed.

Main Results:

• rVEGF dose-dependently increased MC viability and BDNF production under diabetic conditions.
• rBDNF dose-dependently enhanced MC viability.
• TRK-B knockdown significantly reduced phosphorylated AKT and ERK.
• rBDNF rescued MC viability loss in TRK-B siRNA cells under diabetic conditions.
• VEGF was identified as a positive regulator of BDNF production in diabetes.

Conclusions:

• VEGF promotes BDNF production in diabetic conditions, which in turn supports Müller cell viability.
• The BDNF-TRK-B signaling pathway, involving AKT and ERK, mediates MC survival.
• These findings highlight a novel therapeutic avenue for DR and other hypoxic retinal diseases.
• Targeting the VEGF-BDNF axis may improve treatments for DR and related vascular disorders.