VEGF in Diabetic Retinopathy and Age-Related Macular Degeneration

Abstract

Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis throughout the human body, influencing countless physiological and pathological processes, including tumor growth, preeclampsia, and retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). In DR, VEGF promotes retinal neovascularization and intraretinal fluid accumulation, leading to complications like diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Regular intravitreal anti-VEGF injections are commonly used to manage PDR and DME, though repeated treatments are often required, and efficacy can be limited. AMD, a major cause of vision loss in older adults, is characterized by either dry or wet forms. While the dry form has not been shown to be influenced by VEGF, the choroidal neovascularization of wet AMD has strong associations with VEGF. Current treatment for wet AMD consists primarily of anti-VEGF injections, the gold standard of care, but is limited by varying patient responses, as treatments are often repeated every 4-8 weeks indefinitely. This review explores the pathogenic role of VEGF in both DR and AMD, discussing the molecular mechanisms underlying these diseases and the therapeutic approaches targeting VEGF. Despite advancements, the variability in treatment responses highlights the need for continued research to develop more effective therapies to prevent vision loss and blindness associated with these retinal diseases.

Keywords: AMD; DR; Ophthalmology; VEGF; age-related macular degeneration; diabetic retinopathy; vascular endothelial growth factor.

Figure 1

The central role VEGF plays in the development of DR and AMD. Blue arrows are assigned to the AMD pathway, and red arrows are assigned to the DR pathway.

Figure 2

The role of the major pathways of retinal monocytes and microglia activation and polarization in AMD development. Mediators of these pathways include zinc and sialic acid ligation. + denotes a positive influence on that pathway. - denotes a negative influence on that pathway.

Figure 3

Anti-VEGF therapy in wet AMD and DR. Blue arrows are assigned to the AMD pathway, and red arrows are assigned to the DR pathway.