Role of active oxygen species in corneal ulceration. Effect of hydrogen peroxide generated in situ.
Cationic glucose oxidase, prepared by amidation of its free carboxylic groups, has prolonged retention in tissues, resulting in sustained release of hydrogen peroxide generated during oxidation of endogenous glucose. Increased levels of hydrogen peroxide can inhibit superoxide dismutase activity, thereby promoting reduction of transition metal ions, particularly iron and copper, by superoxide anions. Therefore, hydrogen peroxide can generate highly reactive hydroxyl radicals through a superoxide-driven Fenton reaction. Amidated glucose oxidase injected into rabbit cornea produces corneal opacification within 3-4 days and severe corneal damage by 7 days. Ultrastructural studies revealed typical tissue lesions observed in corneal melting. Heat-inactivated amidated glucose oxidase had no effect during the first 3-4 days. However, a gradual opacification occurred thereafter, resulting in some cases, in a severe opacity by 7 days. These results are consistent with an oxidative attack on corneal glycoconjugates by radicals derived from glucose oxidase-generated hydrogen peroxide during the first 3-4 days. Invading phagocytic cells are responsible for lesions observed with the inactive enzyme and for the progression of the initial lesions caused by the active enzyme. Stimulated phagocytic cells not only produce active oxygen species during the respiratory burst, but also release neutral collagenase and acid lysosomal hydrolases that contribute to and amplify the degradation of the extracellular matrix.
Carubelli
R
R
Oklahoma Medical Research Foundation, Oklahoma City 73104.
Nordquist
R E
RE
Rowsey
J J
JJ
D000818:Animals; D002374:Catalase / Q000378:metabolism; D003318:Corneal Opacity / Q000209:etiology / Q000473:pathology; D003320:Corneal Ulcer / Q000209:etiology* / Q000473:pathology; D004789:Enzyme Activation; D005609:Free Radicals; D005949:Glucose Oxidase / Q000008:administration & dosage; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006900:Hydroxylation; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D002374:Catalase; D010100:Oxygen