Photochemically induced cataracts in rat lenses can be prevented by AL-3823A, a glutathione peroxidase mimic.

Abstract

Oiddatve stress is known to cause cataracts In lens culture systems and is believed to be an important factor contributing to human cataracts. In this communication, it is demonstrated that cataract development of cultured rat lenses produced as a result of photochemkaily induced oxidation in a 4% oxygen atmosphere imilar to the native environment ofthe lens can be blocked by the ttion metal complex AL-3823A. In this system, riboflavin is added to the medium as a photosensitizer. AL-3823A acts primarily as a glutathione peroxidase mimic, which catalyticafly metabdoi H202 and also has low superoide dimutaeke activity. Mamsurements of H202,°2 -and OH te that appreciable levels of the first two of these oxidants and low levels of OHf are produced by this photochemical sreing system. The H202 concentrations are milar to those found in some patients with cataracts. The development of cataracts was followed over a 96-hr period.Transparency, hydration, glyceraldehyde-3-phosphate dehydrogenase activy, and protein and nonprotein thiol were monitored. AU parameters show marked chang during the 96-hr period. However, in the presence of 200 pM AL-3823A, no difference between control and light-exposed lenses was observed with respect to these parameters. The results suggest that in Wvo human cataract development caused by oxidative str may be prevented by compounls of this type.One ofthe major problems confronting investigators studying cataracts is that of definitively defining the factors that initiate the loss of opacity. For certain types of cataracts, the relationship between cause and effect is obvious. Thus, in diabetic cataracts, it is generally accepted that osmotic shock induced by the formation of sugar alcohols initiates the development ofopacification (1), and in congenital cataracts, it probably is a genetic defect that causes the pathology (2, 3). Numerous animal models for cataracts have been developed that utilize oxidative or osmotic stress and, in some cases, mutation as the initiating factor (3). However, with maturityonset cataract, a disease that afflicts a majority of people in later life, the causes are difficult to define. It is generally believed that for a significant proportion of this population, oxidative stress is an initiating or major contributing factor (4). This viewpoint is supported by a large body of evidence indicating that (i) oxidants such as H202 can cause cataracts (5, 6), (ii) in some patients, aqueous humor and lens H202 levels are elevated to concentrations that will cause cataracts in model systems (7-9), and (iii) analyses of human cataracts indicate extensive oxidation of lens proteins (10-13) and lipids (14,15

Mice Lacking Catalase Develop Normally but Show Differential Sensitivity to Oxidant Tissue Injury

“…The control lenses were incubated in the same medium but without exposure to light. Previous studies have shown that the photochemical reaction used generates mainly superoxide anion radical and H 2 O 2 and to a much lesser extent hydroxyl radical (41). In addition, development of opacity in lenses following photochemical stress could be prevented by the addition of exogenous catalase, suggesting the pathogenic role of H 2 O 2 in this model of cataract (42).…”

“…Exposure of Lens to Oxidative Stress Generated by Photochemical Reaction-The method for quantifying damage in animal lens following exposure to photochemically induced oxidative stress has been previously described (41)(42)(43). Briefly, lenses were removed from the eyes of Cat ϩ/ϩ and Cat Ϫ/Ϫ mice immediately following sacrifice.…”

Free Radicals and Aging of Anterior Segment Tissues of the Eye: A Hypothesis

“…Recent studies with glutathione peroxidase mimics [37,38] have also shown that they are capable of assist ing in the protection against free radical-in duced damage to lenses. These experiments support the concept that the presence of a com pound that eliminates hydrogen peroxide is suf ficient to prevent cataract development during periods of oxidative stress.…”

Ocimum sanctum extracts attenuate hydrogen peroxide induced cytotoxic ultrastructural changes in human lens epithelial cells

“…This finally results in cataract formation and blindness. Available reports suggest that elimination of H 2 O 2 by antioxidants can prevent cataract formation in cultured animal lenses (Spector et al, 1993) as well as in rabbit lens epithelial cells (Reddan et al, 1993).…”