EFFECT OF VITAMIN E ON LIPIDHYDROPEROXIDE-INDUCED CORNEAL NEOVASCULARIZATION

Takako N. Ueda, Akira Higa*, Yuichiro Arai, Shohei Fukuda*, Toshihiko Ueda, Donald Armstrong*, Hajime Yasuhara, Ryohei Koide*

Dept of Pharmacology and *Dept of Ophthalmology, School of Med. Showa Univ. Tokyo 142-8555, Japan

The purpose of this study is to compare the effects of vitamin E (VE) on corneal neovascularization induced by linoleic acid hydroperoxide (LHP) between the normal rabbits and the hyperglycemia one. (T.Ueda, Angiogenesis 1: 174-184, 1997 ). Rabbits were divided into 4 groups, C; New Zealand rabbits (NZ) as control (n=5), C+E; NZ with VE treatment (n=3), HG; hyperglycemia above 200 mg/dl by 80 mg/kg alloxan i.v.(n=10) and HG+E; HG with VE treatment (n=3). One week after HG condition, rabbits were fed chow (RC4; Oriental Yeast Co., Ltd., Tokyo) with or without 0.02% VE for 3 wks. Next, 10μl of LHP (40 mM) synthesized from lipoxygenase was injected with a 30 ga needle positioned under a  Zeiss operating microscope. Vessel growth area from the limbal vasculature was measured over a period of 2 wks. Neovascularization was observed in the superior segment of the cornea and grew towards the injection site. At 14 days post-injection, the longest vessel length were 1.17±0.09 mm in C, 1.07±0.24 mm in C+E, 1.92±0.31 mm in HG, 1.40±0.14 mm in HG+E. VE inhibited LHP-induced corneal neovascularization. The LHP-induced neovascular response was  markedly enhanced in the high glucose animals. These data suggest that hyperglycemia sensitizes corneal and endothelial cells, probably by glucose derived radicals, which enhance production of additional LHP and angiogenìc cytokines through more rapid propagation reactions, raising the concentration levels to induce an enhanced, sustained neovascularization.