Total antioxidant capacity in Eales' disease, uveitis & cataract

Cells and biological fluids in the human system have an array of protective antioxidant mechanisms, both for preventing the production of free radicals (O2•, OH•, ROO•, RO•, NO•) and for repairing oxidative damage1,2. Any imbalance due to an excess oxidant formation or lowered antioxidants leads to an oxidative stress damaging lipids, proteins and nucleic acids which leads to inflammation followed by tissue injury and cell death. To assess the status of oxidative stress, it is usually necessary to estimate the oxidants markers and the antioxidant parameters. TBARS (Thiobarbituric acid reactive substances) are direct markers of oxidative stress. The antioxidant parameters that can be analyzed are the non-enzymatic ones like vitamin A, E and C, glutathione, apart from the enzymatic ones like catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx). To study all these parameters is tedious, time consuming and uneconomical. To replace the analysis of the various antioxidants with a single test, the total antioxidant capacity (TAC) assay is done in normal and pathological conditions3,4. According to the method by Koracevic et al5 TAC measures predominantly low molecular weight, chain breaking antioxidants (urate, ascorbate, bilirubin, albumin and thiols in the aqueous phase and α-tocopherol, carotenoids, and flavonoids in the lipid phase), excluding the contribution of antioxidant enzymes and metal binding proteins. The ability of the antioxidants to suppress the formation of TBARS by OH•, is called direct inhibition by antioxidants and TAC assay is a direct inhibition assay. Oxidative stress is considered a major factor contributing to the pathogenesis of the Eales’ disease (ED) which is a relatively rare disease observed in the Indian subcontinent in healthy adult males6,7. ED is an idiopathic inflammatory venous occlusion that primarily affects the peripheral retina of adults8. Stages of ED broadly include stage of retinal phlebitis, stage of peripheral nonperfusion, and stage of retinal neovascularization7. Previous work in our laboratory has proved the role of free radicals in increasing the markers of lipid peroxidation namely, TBARS9,10, protein oxidation products as carbonyl content11, nitrotyrosine12 and DNA oxidative products as 8-hydroxy guanosine in ED13,14. Oxidative stress has also been reported in the platelets of Eales’ disease cases15,16. Uveitis is another inflammatory process involving the anterior segment of the eye. Inflammation of the uvea is termed iridocyclitis. In uveitis, metabolites of oxygen-free radicals generated by polymorphonuclear leukocytes and macrophages are believed to inflict the initial tissue damage in acute inflammation17. Studies have shown the involvement of superoxide, nitric oxide and peroxynitrite in experimental autoimmune uveitis18. While ED and uveitis involve acute and active periods of inflammation and oxidative stress, cataract is more of a chronic condition exhibiting oxidative stress with ageing. Cataract formation is one of the many destructive changes that can occur with overproduction of oxidants, possibly due to deficiency of an important protective antioxidant called glutathione. Glutathione occurs in high levels in the eye and helps clean up these free radicals. One theory posits that in the ageing eye, barriers develop that prevent glutathione and other protective antioxidants from reaching the nucleus in the lens, thus making it vulnerable to oxidation19,20. Since TAC measurement can provide a quick tool for establishing a link between oxidant stress and the severity of the disease as well as in monitoring of antioxidant therapy, the present study was aimed to estimate the serum total antioxidant capacity (TAC) and compare it with individual antioxidants such as glutathione (GSH), vitamin E and C apart from the oxidative stress marker TBARS in ocular inflammatory diseases such as Eales’ disease, in a more acute inflammatory condition as in uveitis as well as in cataract that is more chronic, in comparison to healthy controls.