Retinal vascular development and oxygen-induced retinopathy: A role for adenosine

Gerard Anthony Lutty, D. Scott McLeod

Research output: Contribution to journalArticle

Abstract

Adenosine is a ubiquitous molecule that is produced predominantly by catabolism of adenosine triphosphate. Levels of this nucleoside increase dramatically with ischemia and elevated tissue activity. Adenosine levels are high in inner retina during retinal vascular development in postnatal dog. The source appears to be the ectoenzyme 5′ nucleotidase, which is prominent at this time in the innermost process of Muller cells. One of the adenosine receptors, A2A, is present on endothelial cell precursors, angioblasts, and endothelial cells in formed blood vessels in neonatal dog. These observations suggest that adenosine is important in retinal vascular development. Oxygen-induced retinopathy (OIR) is a model for human retinopathy of prematurity (ROP). The initial event in OIR is induced by exposure of the developing retina to high oxygen. Vascular development is halted and over 60% of the retinal vasculature is lost during this stage of the disease in dog, which is called vaso-obliteration. 5′ nucleotidase is dramatically reduced during vaso-obliteration, resulting in a sharp decline in adenosine. When animals are returned to room air, the retina is hypoxic because of the lack of blood vessels, oxygen consumption is increased due to neuronal development, and systemic levels of oxygen have returned to normal. At this time, 5′ nucleotidase activity and adenosine levels are elevated well beyond normal levels. This stage of OIR is the vasoproliferative stage and A2A expression and endothelial cell proliferation are very elevated compared to control animals. Florid preretinal neovascularization forms, which has high levels of adenosine and A2A receptors. Therefore, adenosine and its A2A receptor appear to be important in canine OIR. This work suggests that adenosine and its receptors may be a therapeutic target in OIR. This hypothesis is supported by recent studies in mouse (Mino et al., Invest. Ophthalmol. Vis. Sci. 42(13) (2001) 3320), which demonstrated that targeting one of the A2 receptors can inhibit formation of neovascularization in OIR.

Original languageEnglish (US)
Pages (from-to)95-111
Number of pages17
JournalProgress in Retinal and Eye Research
Volume22
Issue number1
DOIs
StatePublished - Jan 2003

Fingerprint

Retinal Vessels
Adenosine
Oxygen
Adenosine A2A Receptors
5'-Nucleotidase
Blood Vessels
Retina
Endothelial Cells
Dogs
Dog Diseases
Ependymoglial Cells
Retinopathy of Prematurity
Purinergic P1 Receptors
Nucleosides
varespladib methyl
Oxygen Consumption
Canidae
Ischemia
Adenosine Triphosphate
Air

ASJC Scopus subject areas

  • Sensory Systems
  • Ophthalmology

Cite this

Retinal vascular development and oxygen-induced retinopathy : A role for adenosine. / Lutty, Gerard Anthony; McLeod, D. Scott.

In: Progress in Retinal and Eye Research, Vol. 22, No. 1, 01.2003, p. 95-111.

Research output: Contribution to journalArticle

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