Inhibition of intraocular neovascularization caused by retinal ischemia in pigs by PKCbeta inhibition with LY333531.

摘要: OBJECTIVE: The authors tested the antiangiogenic properties of an orally administered protein kinase-Cbeta inhibitor, LY333531, in a pig model preretinal neovascularization caused by retinal branch vein occlusion to determine effectiveness this therapy preventing intraocular from ischemic stimulus. METHODS: In 20 eyes 10 pigs, occlusions were created standardized manner using photodynamic thrombosis with rose bengal dye and thermal burns argon laser green light. Five animals received 1 mg/kg LY333531 daily two oral doses, five untreated. followed clinically for 12 weeks ophthalmoscopy, fundus photography, fluorescein angiography. A grading system permitted masked assessment disc proliferations stereo photographs. After pigs killed, all was confirmed histopathologically fashion final grade assigned each eye. Mann-Whitney test used statistical analysis median values unpaired data between animal (data rounded up). RESULTS: Significant inhibition observed treated study drug (P = 0.03). Although some demonstrated no evident new vessels, histopathologic photographic fine vessels on optic (mean 1.9). All untreated developed 3.1). well tolerated, side effects documented. CONCLUSIONS: specific effectively inhibited nerve head occlusion. This consistent known pathways signal transduction growth factors activated cells suggested that key regulatory isozyme is effective treatment ischemia-mediated neovascular diseases.