Abstract
Purpose :
Vascular endothelial growth factor (VEGF or VEGF-A), a major therapeutic target for blood-retina barrier breakdown (BRB) in diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD), has been shown to act as a direct functional regulator for peripheral and central nervous system (CNS) neurons. The purpose of this study was to determine whether VEGF is a direct regulator of photoreceptor function and its potential role in altering vision during the progression of DR, AMD, and other hypoxic retinal BRB diseases.
Methods :
For this study, we developed a procedure to measure the direct effect of VEGF on photoreceptor function with electroretinography (ERG). Overnight dark-adapted wild-type (WT) mice were injected with recombinant VEGF (rVEGF) intravitreally under long-wavelength illumination. Retinal function in these mice was examined with scotopic and photopic electroretinography ERG immediately after intravitreal rVEGF delivery. Diabetes- or hypoxia-induced alteration of photoreceptor function was examined with Akita diabetic mice or hypoxic mice immediately after injected with rVEGF or vehicle.
Results :
In dark-adapted WT mice, rVEGF caused a significant reduction of scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes in a dose-dependent manner. However, the effect of rVEGF on the alteration of ERG amplitudes was nullified in 5-mo-old Akita diabetic mice in which a higher level of VEGF was present in photoreceptors. A similar result was also observed in 1.5 mo-old hypoxic mice generated by placing the animals with 7% oxygen for 5 days.
Conclusions :
Our results suggest that VEGF is a direct functional regulator for photoreceptors and a contributing factor to the loss of photoreceptor function in diabetes and hypoxia (retinal environment in AMD). As VEGF is a major therapeutic target for BRB breakdown in DR, AMD, and other hypoxic retinal BRB diseases, our work provides the mechanistic insights for the therapeutic effects on visual acuity and for the care of anti-VEGF drug treated patients.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.