Glycated proteins can enhance photooxidative stress in aged and diabetic lenses.
This study intends to clarify the ability of different carbonyl-containing lens metabolites to form advanced glycation end products, which possess photosensitizer activity and to investigate whether these modified proteins could be implicated in lens photodamage. Calf lens protein was experimentally glycated with either methylglyoxal, glyoxal, ascorbic acid, or fructose to obtain models of aged and diabetic cataractous lenses. Being exposed to 200J/cm2 UVA radiation the model glycated proteins produced 2-3-fold more singlet oxygen compared to the unmodified protein and the superoxide radical formation was 30-80% higher than by the native protein. Ascorbylated proteins demonstrated the highest photosensitizer activity. Biological responses of glycation-related photosensitizers were studied on cultured lens epithelial cells irradiated with 40J/cm2 UVA. Tissue culture studies revealed a significant increase in thiobarbituric acid reactive substances in the culture medium of lens epithelial cells after irradiation and treatment with glycated proteins. Lens proteins had a protective effect against UVA induced cytotoxicity, however, this protective effect decreased with the increasing photosensitizer activity of experimentally glycated proteins. The documented glycation-related photosensitization could explain the accelerated pathogenic changes in human lens at advanced age and under diabetic conditions.
Argirova
Mariana D
MD
Department for Experimental Ophthalmology, University of Bonn, Abbéstr. 2, 53105 Bonn, Germany. margirova@hotmail.com
Breipohl
Winrich
W
D000375:Aging; D000818:Animals; D002417:Cattle; D002470:Cell Survival; D046508:Culture Techniques; D003921:Diabetes Mellitus, Experimental; D007525:Isoelectric Focusing; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism; D008027:Light; D015227:Lipid Peroxidation; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D017319:Photosensitizing Agents / Q000494:pharmacology; D011134:Polysaccharides / Q000378:metabolism*; D017382:Reactive Oxygen Species; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors; D014466:Ultraviolet Rays
D017319:Photosensitizing Agents; D011134:Polysaccharides; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D007770:L-Lactate Dehydrogenase; D010100:Oxygen