Retinal neovascularization is suppressed with a matrix metalloproteinase inhibitor.
OBJECTIVE
To determine the role of extracellular proteinases in ischemia-induced retinal neovascularization in an animal model and to examine the effect of proteinase inhibitors on retinal neovascularization.


METHODS
Retinal neovascularization was induced in newborn mice exposed to 75% oxygen for 5 days, followed by room air. Retinal extracts underwent zymographic analysis to measure the activity of urokinase and matrix metalloproteinases (MMPs). Some animals under the same conditions also received intraperitoneal injections of an MMP inhibitor. Histological analysis was done to quantitate the neovascular response in these animals.


RESULTS
Levels of urokinase and MMPs (MMP-2 and MMP-9) in retinas were significantly increased in animals with induced retinal neovascularization. Neovascularization was significantly inhibited with intraperitoneal administration of an MMP inhibitor.


CONCLUSIONS
Systemic inhibition of MMPs may have therapeutic potential in preventing retinopathy associated with retinal neovascularization.


CONCLUSIONS
Because up-regulation and activation of proteinases represents a final common pathway in the process of retinal neovascularization, pharmacological intervention of this pathway may be an alternative therapeutic approach to proliferative retinopathy.
Das
A
A
Division of Ophthalmology, University of New Mexico School of Medicine, and Veterans Affairs Administration Medical Center, Albuquerque 87131, USA. adas@unm.edu
McLamore
A
A
Song
W
W
McGuire
P G
PG
D000818:Animals; D000831:Animals, Newborn; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D018093:Gelatinases / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000150:complications; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015861:Retinal Neovascularization / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects* / Q000473:pathology; D013876:Thiophenes / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9