Effects of allopurinol and steroids on inflammation and oxidative tissue damage in experimental lens induced uveitis: a biochemical and morphological study.

AIMS: To evaluate the effects of allopurinol in lens induced uveitis (LIU) by morphological methods and to compare these effects with those of steroids and a combination of both drugs biochemically and morphologically. METHODS: Lipid peroxides (LPO) of the retinal tissue were determined by two different methods (thiobarbituric acid assay (TBA) and high performance liquid chromatography expressed as malondialdehyde-like substances). Myeloperoxidase (MPO) activity in the iris/ciliary body complex was analysed spectrophotometrically. Histological changes on three morphological levels of LIU eyes were evaluated. RESULTS: Both allopurinol and the combination of allopurinol/prednisolone led to a significant reduction in the increaed retinal LPO values. Prednisolone only revealed significant effects on retinal LPO when being measured with the TBA method. MPO activity in iris and ciliary body was significantly reduced in all therapy groups. The morphological evaluation of the sections by two masked investigators revealed a significant reduction (p < 0.05) in the inflammation score in all therapy groups. Morphometric studies using the QUANTIMED system (Leica, Cambridge) showed significantly reduced values (p < 0.05) in the allopurinol group and in the group receiving prednisolone and allopurinol. Prednisolone alone did not lead to a significant reduction in the values. CONCLUSIONS: The findings show that both allopurinol and steroids exert positive effects on the variables determined in LIU. The effects of steroids are believed to be mostly due to their direct action on inflammatory cells. The recently reported scavenging effects of methylprednisolone should play a minor role in this disease model. Allopurinol and oxypurinol act as direct scavengers of free radicals and hypochlorous acid, which is produced via MPO catalysis, thus leading to a reduction in tissue inflammation and tissue damage.

Free radical scavenging and antioxidant activity of allopurinol and oxypurinol in experimental lens-induced uveitis.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The retinal irradiance and spectral properties of the multiport illumination system for vitreous surgery.

The multiport illumination system was developed as a fiberoptically illuminated pars plana cannula system for vitreous surgery. The retinal irradiance of the multiport illumination system and several other commonly used endoilluminators (light pipes) measured at 5 mm are comparable, ranging from 94 to 256 mW/cm2. In the actual surgical setting, however, the retinal irradiance of the multiport illumination system is far less (56 mW/cm2) because the end of the fiberoptic cables are fixated in the pars plana 16.5 mm away from the retinal surface. A reduction in the maximal intensity (100%) to 50% reduces the retinal irradiance by approximately two thirds to 3.7 mW/cm2. The light emitted by the multiport illumination system used in conjunction with a long-wave pass filter with a cutoff wavelength of 420 nm reduces the amount of short-wavelength light by one third to about 4% of the overall irradiance.