Choroidal Neovascularization: Mechanisms of Endothelial Dysfunction

Abstract

Many conditions affecting the heart, brain, and even the eyes have their origins in blood vessel pathology, underscoring the role of vascular regulation. In age-related macular degeneration (AMD), there is excessive growth of abnormal blood vessels in the eye (choroidal neovascularization), eventually leading to vision loss due to detachment of retinal pigmented epithelium. As the advanced stage of this disease involves loss of retinal pigmented epithelium, much less attention has been given to early vascular events such as endothelial dysfunction. Although current gold standard therapy using inhibitors of vascular endothelial growth factor (VEGF) have achieved initial successes, some drawbacks include the lack of long-term restoration of visual acuity, as well as a subset of the patients being refractory to existing treatment, alluding us and others to hypothesize upon VEGF-independent mechanisms. Against this backdrop, we present here a nonexhaustive review on the vascular underpinnings of AMD, implications with genetic and systemic factors, experimental models for studying choroidal neovascularization, and interestingly, on both endothelial-centric pathways and noncell autonomous mechanisms. We hope to shed light on future research directions in improving vascular function in ocular disorders.

Microglia Contribution to the Regulation of the Retinal and Choroidal Vasculature in Age-Related Macular Degeneration

“…Several mechanisms are known to be involved in endothelial dysfunction in the retina and choroidal neovascularization in AMD, such as oxidative stress and chronic inflammation [122]. Nitric oxide is produced by three nitric oxide synthase isoforms (endothelial, neuronal and inducible) that are expressed to variable degrees in the retina [123].…”

Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

“…In addition to the VEGF mechanism, vascular endothelial dysfunction is considered a crucial event in the development and progression of choroidal vascular dysfunction [ 151 ]. Nitric oxide synthases (NOSs) are a family of enzymes that catalyze nitric oxide (NO) production from L-arginine, and are classified into three isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS) [ 152 ].…”

Potential of Telomerase in Age-Related Macular Degeneration—Involvement of Senescence, DNA Damage Response and Autophagy and a Key Role of PGC-1α

“…Choroidal neovascularization (CNV) is an essential process in the pathogenesis of wet AMD, which may lead to permanent vision loss if not treated [20]. CNV is featured by abnormal intravasation of choroidal vessels into the RPE or subretinal tissue, which usually leaks and accumulates blood and other fluids in the macula [21].…”