Various types of insults to the eye such as trauma, immunological derangements, infections and keratomalacia cause ocular lesions which can progress to corneal ulceration (""""""""corneal melting"""""""") and loss of vision. This research proposal is designed to test the hypothesis that the initial lesion(s) caused by these diverse etiologic factors are oxidative modifications of corneal glycoconjugates by active oxygen species. Recent studies on the effect of various active oxygen species (hydrogen peroxide, superoxide anion, hydroxyl peroxide, singlet oxygen) at the molecular level have shown that they can cause oxidative modification of the glycosidic and/or peptidic moieties of glycoconjugates. These oxidative modifications can result in direct degradation of the glycoconjugates by scission of covalent bonds, as well as in chemical modifications that render the glycoconjugates susceptible to degradation by tissular hydrolytic enzymes, which normally do not digest the native compounds.
The specific aims i nclude three groups of studies with experimental systems of different degree of complexity: 1) Investigation of the nature and extent of the oxidative modification of selected corneal glycoconjugates (glycoproteins, keratan sulfate I proteoglycan and collagen) by active oxygen species. These experiments will be carried out with individual glycoconjugates and with mixtures of defined composition; 2) Studies with perfused corneal preparations from normal rabbit eyes and from eyes undergoing corneal ulceration following corneal thermal cauterization in order to correlate biochemical and morphological alterations in an organized tissue under defined experimental conditions; and 3) Investigation of the effect of antioxidants, glutathione, active oxygen scavengers (including spin trapping agents) in order to gain an insight into possible approaches to the prevention, halting, or reversal of corneal melting.
| Chace, K V; Carubelli, R; Nordquist, R E (1991) The role of nonenzymatic glycosylation, transition metals, and free radicals in the formation of collagen aggregates. Arch Biochem Biophys 288:473-80 |
| Chace, K V; Carubelli, R; Nordquist, R E et al. (1991) Effect of oxygen free radicals on corneal collagen. Free Radic Res Commun 12-13 Pt 2:591-4 |
| Carubelli, R; Nordquist, R E; Rowsey, J J (1990) Role of active oxygen species in corneal ulceration. Effect of hydrogen peroxide generated in situ. Cornea 9:161-9 |
