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For evaluation of the effects of different free-radical scavengers on biochemical changes in lens-induced uveitis (LIU), ten male Wistar rats were sensitized for 8 weeks using bovine lens protein and Freund's adjuvant. The uveitis was induced by disruption of the lens capsule. One group of animals received superoxide dismutase and catalase (SOD/CAT); a second group of animals was treated with vitamin E. Lipid peroxides (LPO) of the retinal tissue and aqueous humor served as parameter of oxidative tissue damage. Glutathione (GSH/GSSG) of the aqueous humor was evaluated as a parameter of the tissue's redox state. For evaluation of the inflammatory response, myeloperoxidase activity (MPO) was determined in the iris/ciliary-body complex. SOD/CAT produced no improvement in the significantly (P0.05) elevated MPO and LPO values recorded for untreated control animals. Following vitamin E treatment the GSH/GSSG and LPO values in aqueous humor were markedly improved as compared with controls. Retinal LPO values were significantly (P0.05) reduced as compared with controls. No change in MPO levels was observed. The results demonstrate that enzymes such as SOD and CAT do not influence tissue damage at a significant level, whereas radical chain breakers such as vitamin E can do so. However, the inflammatory response itself is not reduced. To achieve global results, drugs are necessary that act on both free radicals produced by noninflammatory pathways and those originating from inflammation.

In 153 eyes with idiopathic posterior subretinal neovascularization (IPSN) and myopia of no greater than −6 dpt, the relative risk of this disorder was determined with regard to refraction. It was shown that the probability of developing this condition is directly proportional to the degree of myopia. By using data obtained from the literature for calculating the relative risk regarding refraction, it was demonstrated that the same is true for subretinal neovascularization in degenerative myopia greater than −7.5 dpt (Fuchs' spot). The relative risk for developing one of both disorders increases exponentially with increasing myopia.

To evaluate whether oxidative tissue damage and inflammatory reactions occur in epiretinal membranes of eyes suffering from proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), and macular pucker (MP).Epiretinal membranes were removed during surgery and frozen at -80 degrees C (PDR, n = 26; PVR, n = 24; MP, n = 15), and oxidative tissue damage and inflammatory activity (MPO) of the membrane tissue were determined. The values are expressed as means of thiobarbituric acid-reactive substances (TBARS, nmol/mg) and MPO (units/mg).Both TBARS and MPO activity were significantly elevated (P0.05) in membranes of eyes suffering from PVR and PDR compared to MP. The myeloperoxidase activity in PDR membranes was significantly increased (P0.05) compared to PVR.Inflammatory cells and oxidative metabolites lead to oxidative reactions in PDR and PVR. The proliferation of membrane tissue may be enhanced through products of the lipoxygenase pathway, which is active in inflammatory cells and leads to oxidative tissue damage. Chemoattraction of leukocytes by oxidative metabolites renders the process self-progagating. Since patients suffering from MP have an intact vitreous body with an intact antioxidative system, this reaction occurs to a lesser degree, resulting in less membrane-growth activity. The cell-growth-enhancing properties of inflammatory cells should be further investigated in PDR and PVR with regard to new therapeutic interventions.

In addition to the inhibition of xanthine oxidase, allopurinol is known to act, dependent on the dose, as a free radical scavenger, an antioxidant, and a "scavenger" of hypochlorous acid. This activity was investigated using a model of lens-induced uveitis.Lipid peroxides (LPO) were determined in aqueous humor and in retinal tissue. Reduced and oxidized glutathione (GSH and GSSG) of the aqueous humor and myeloperoxidase (MPO) activity in the iris-ciliary body complex were analyzed. Allopurinol and oxypurinol concentrations were determined by high-performance liquid chromatography in aqueous humor and retinal tissue of both control eyes and eyes with uveitis. These measurements were performed 6 hours after intravenous application of allopurinol.In lens-induced uveitis, LPO are significantly elevated, GSH is reduced, and GSSG and MPO are increased. A xanthine oxidase inhibition dose (10 mg/kg body weight) of allopurinol showed no effects on oxidative tissue damage in the model used in this study. Higher doses, however, were able to reduce the oxidative damage. Allopurinol (20 mg/kg body weight) had slight effects on GSH and GSSG. All parameters improved using a dose of 50 mg/kg body weight; a dose of 100 mg/kg body weight only showed additional improvement in GSH and GSSG. There was no further change in the other parameters. Allopurinol and oxypurinol concentrations in aqueous humor and retinal tissue showed a dose dependency reaching scavenger concentrations after application of 50 mg/kg body weight of allopurinol.These results suggest that the xanthine oxidase mechanism plays a minor role in the oxidative tissue damage due to lens-induced uveitis. Free radicals and oxidants are generated by activated leukocytes; therefore, the effect of higher doses of allopurinol is due to its free radical scavenging and antioxidative activity.