Understanding ischemic retinopathies: emerging concepts from oxygen-induced retinopathy.
Ischemic retinopathies, such as retinopathy of prematurity and diabetic retinopathy are characterized by an initial microvascular degeneration, followed by an abnormal hypoxia-induced neovascularization. Oxygen-induced retinopathy (OIR) is a well-established in vivo model of ischemic retinopathies, which, although the triggering insult varies, all share a common end result of capillary loss. Understanding the mechanisms of normal retinal vascular development as well as the pathophysiological processes leading to the primary vascular loss is the key to develop treatments to prevent the sight-threatening neovascularization associated with human ischemic retinopathies. The importance of oxygen-dependent vascular endothelial growth factor in the pathophysiology of both phases of OIR has long been recognized. However, recent studies point out that OIR is a multifactorial disease, resulting from additive effects of an unbalanced expression of pro- and anti-angiogenic factors, interrelated with protective effects of nutritional factors and cytotoxic effects of oxidative and nitro-oxidative stress-dependent mediators. This review summarizes the most recent aspects of the research on OIR conducted in our laboratory and others, with a particular focus on the role of new mediators of nitro-oxidative stress, the trans-arachidonic acids, in microvascular degeneration, and on a novel pathway of metabolic signaling where hypoxia-driven succinate, via receptor GPR91, governs normal and pathological retinal angiogenesis.
Kermorvant-Duchemin
Elsa
E
INSERM UMRS 872, Paris, France.
Sapieha
Przemyslaw
P
Sirinyan
Mirna
M
Beauchamp
Martin
M
Checchin
Daniella
D
Hardy
Pierre
P
Sennlaub
Florian
F
Lachapelle
Pierre
P
Chemtob
Sylvain
S
D000818:Animals; D003930:Diabetic Retinopathy / Q000209:etiology*; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D007511:Ischemia / Q000209:etiology*; D018384:Oxidative Stress; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000209:etiology*
D010100:Oxygen