PURPOSE: The efficacy of three matrix metalloproteinase (MMP) inhibitors with various selectivities ( @entity53278 , @entity65220 , and @entity70248 ) was investigated in a @entity35 model of @entity989 , to examine the roles of @entity33238 in @entity2479 . The susceptibilities of @entity5780 (-/-) and -9(-/-) @entity19 to preretinal neovascularization were investigated in a @entity19 model of @entity26 -induced @entity989 . METHODS: Sprague-Dawley newborn @entity35 were exposed to alternating episodes of 50% and 10% @entity26 (variable @entity26 exposure) to induce @entity2479 . Three MMP inhibitors with various selectivity profiles were administered to variable @entity26 -exposed @entity35 via local or systemic routes. Antineovascular efficacy was determined in drug-treated versus vehicle-treated @entity35 pups by computerized imaging of @entity859 diphosphatase (ADPase)-stained retinal flatmounts. Wild-type C57BL/6J and isogenic @entity5780 (-/-) and -9(-/-) @entity19 were exposed to 75% @entity26 followed by normoxia. The @entity19 were killed immediately before or after the normoxic exposure, and eyes were either harvested for retinal dissection and flatmounting or were paraffin embedded and sectioned. @entity2479 were assessed by @entity859 diphosphatase staining of retinal flatmounts and by counting preretinal nuclei of @entity1710 and @entity1711 -stained retinal sections, respectively. RESULTS: @entity53278 , @entity65220 , and @entity70248 had no effect on normal development of the @entity35 retinal vasculature, regardless of dose or route of administration. Intravitreal injection of @entity53278 (broad-spectrum) immediately after variable- @entity26 exposure and 2 days after exposure resulted in 78% and 82% inhibition of @entity2479 , respectively. @entity65220 ( @entity5780 - and -9-selective inhibitor) and @entity70248 ( @entity5780 -selective inhibitor) resulted in 65% and 52% inhibition, respectively, when administered by intravitreal injection immediately after variable- @entity26 exposure. Intraperitoneal injection of 5, 15, and 50 mg/mL @entity65220 or @entity70248 for 6 days after variable @entity26 exposure resulted in 22% to 39% and 0% to 31% inhibition of neovascularization, respectively. @entity65220 and @entity70248 administered by oral gavage at doses of 3, 10, or 30 mg/mL provided up to 42% and 86% inhibition of neovascularization, respectively. The average vascular areas of retinas from @entity5780 (-/-) or -9(-/-) @entity19 at postnatal day 12 were not significantly different from the wild-type control. There was a 75% (P < 0.001) and 44% (P < 0.01) reduction in preretinal neovascularization in @entity26 -exposed @entity5780 (-/-) and -9(-/-) @entity19 at postnatal day 19, respectively, compared with wild-type control @entity19 . CONCLUSIONS: The results of this study suggest that @entity5780 plays a predominant role in retinal angiogenesis in both the @entity19 and @entity35 models of @entity26 -induced @entity989 . Furthermore, @entity5780 inhibition may be a viable therapeutic approach for @entity2194 characterized by @entity2479 .

Pharmacologic and genetic manipulation of MMP-2 and -9 affects XXXX in rodent models of OIR.

@entity65220 :: ('MESH:C113282', 'Chemical') :: ['AG3340'] @entity2194 :: ('MESH:D005128', 'Disease') :: ['ocular diseases'] @entity70248 :: ('MESH:C517488', 'Chemical') :: ['DPC-A37668'] @entity859 :: ('MESH:D000241', 'Chemical') :: ['adenosine'] @entity2479 :: ('MESH:D012173', 'Disease') :: ['retinal neovascularization', 'Retinal vascular area and retinal neovascularization'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity5780 :: ('17390(Tax:10090)', 'Gene') :: ['MMP-2'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity1711 :: ('MESH:D004801', 'Chemical') :: ['eosin'] @entity53278 :: ('MESH:C097661', 'Chemical') :: ['Ro-31-9790'] @entity1710 :: ('MESH:D006416', 'Chemical') :: ['hematoxylin'] @entity989 :: ('MESH:D012164', 'Disease') :: ['retinopathy', 'retinopathy of prematurity'] @entity35 :: ('10116', 'Species') :: ['rat', 'rats'] @entity33238 :: ('81686;81687', 'Gene') :: ['MMP-2 and -9']
@entity2479 :: (MESH:D012173,Disease) :: ['retinal neovascularization']
