TY - JOUR
T1 - Retinal vascular development and oxygen-induced retinopathy
T2 - A role for adenosine
AU - Lutty, Gerard A.
AU - McLeod, D. Scott
N1 - Funding Information:
The authors acknowledge their collaborators, Makoto Taomoto, M.D., and Carol Merges, M.E.S., who contributed substantially to the studies discussed in this manuscript, Andrew Newby, M.D., for his generosity in providing the antibody against adenosine, and Maria Grant for helpful discussions about adenosine. This work was supported by NIH grants EY 01765 (Wilmer Institute) and EY09357 (GL), the ROPARD Foundation, and the Brownstein Foundation. Gerard A. Lutty is an American Heart Association Established Investigator and the recipient of a Research to Prevent Blindness Lew Wasserman Merit Award.
PY - 2003/1
Y1 - 2003/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S1350-9462(02)00058-7
DO - 10.1016/S1350-9462(02)00058-7
M3 - Review article
C2 - 12597925
AN - SCOPUS:0037280139
SN - 1350-9462
VL - 22
SP - 95
EP - 111
JO - Progress in Retinal Research
JF - Progress in Retinal Research
IS - 1
ER -