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Understanding ischemic retinopathies: emerging concepts from oxygen-induced retinopathy

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Abstract

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-dependant 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-dependant 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.

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Abbreviations

AA:

Arachidonic acid

DHA:

Docosahexaenoic acid

EPO:

Erythropoietin

HIF:

Hypoxia-induced factor

IGF-1:

Insulin-like growth factor-1

IGFBP-3:

Insulin-like growth factor binding protein-3

MAPK:

Mitogen-activated protein kinase

OIR:

Oxygen-induced retinopathy

NO:

Nitric oxide

PUFA:

Poly-unsaturated fatty acids

RGCs:

Retinal ganglion cells

ROP:

Retinopathy of prematurity

TAA:

Trans-arachidonic acids

TSP-1:

Thrombospondin-1

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This work was supported by grants form the Canadian Institutes of Health Research (CIHR), the March of Dimes Birth Defects Foundation, the Heart & Stroke Foundation of Québec, the Fonds de la Recherche en Santé du Québec and INSERM (France). SC also holds two Canada Research Chairs (perinatology and ophthalmology).

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Authors and Affiliations

  1. INSERM UMRS872, Paris, France

    Elsa Kermorvant-Duchemin & Florian Sennlaub

  2. Paris Descartes University, Paris, France

    Elsa Kermorvant-Duchemin & Sylvain Chemtob

  3. AP-HP, Paris, France

    Elsa Kermorvant-Duchemin & Florian Sennlaub

  4. Department of Pediatrics, Ophthalmology, and Pharmacology, Research Center, Sainte-Justine Hospital, Montreal, QC, Canada

    Przemyslaw Sapieha, Mirna Sirinyan, Martin Beauchamp, Daniella Checchin, Pierre Hardy & Sylvain Chemtob

  5. University of Montreal, Montreal, QC, Canada

    Pierre Hardy & Sylvain Chemtob

  6. Department of Ophthalmology, McGill University-Montreal Children’s Hospital, Montreal, QC, Canada

    Pierre Lachapelle

  7. Department of Pediatrics and Pharmacology, Research Center, Sainte-Justine Hospital, University of Montreal, Montreal, QC, H3T 1C5, Canada

    Sylvain Chemtob

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  1. Elsa Kermorvant-Duchemin
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  2. Przemyslaw Sapieha
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Correspondence to Sylvain Chemtob.

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Kermorvant-Duchemin, E., Sapieha, P., Sirinyan, M. et al. Understanding ischemic retinopathies: emerging concepts from oxygen-induced retinopathy. Doc Ophthalmol 120, 51–60 (2010). https://doi.org/10.1007/s10633-009-9201-x

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