allopurinol and Retinal-Diseases

The eye is at high risk to be damaged by oxidative mechanisms. One major reason is the exposure to light throughout life. Anterior segment structures are mostly exposed to UV light. Visible blue light is believed to be a significant damaging mechanism for the retina. The biochemical composition of the posterior segment structures (unsaturated fatty acids) is an important factor making the eye more susceptible than other organs. Damaging mechanisms such as xanthin oxidase mechanisms are responsible for damage occurring in ischaemic diseases. These mechanisms are well known from diseases of other organs. Ischaemic processes are no longer believed to be the primary damaging mechanisms in diabetic retinopathy. Here, advanced glycation end products (AGE's) and related products may induce oxidative reactions and the expression of growth factors. In age-related macular degeneration photodynamic processes occurring already in childhood are believed to be a major factor contributing to the pathogenesis of the disease process. In addition, the expression of growth factors and new vessel growth can be initiated via inflammatory reactions or oxidative metabolites. In this manuscript we give an overview on oxidative mechanisms involved in the pathogenesis of retinal diseases. Different therapeutical and preventive approaches such as the results of the ARED-Study and possible side effects are discussed.

Topics: Adult; Aged; Child; Glycation End Products, Advanced; Humans; Lipid Peroxidation; Macular Degeneration; Oxidative Stress; Retina; Retinal Diseases; Risk Factors; Ultraviolet Rays; Xanthine Oxidase

Topics: Allopurinol; Humans; Retinal Diseases

Topics: Adult; Allopurinol; Crystallization; Diagnostic Techniques, Ophthalmological; Female; Gout Suppressants; Humans; Retina; Retinal Diseases; Tomography, Optical Coherence; Visual Acuity

This study was planned to investigate the neuroprotective potentials of three commercially available prostaglandin analogues (PGA), in the ischemia and reperfusion model (I/R). Thirty New Zealand rabbits were divided into 5 groups and except for the control group (non-ischemic, non-treated), 0.9% NaCl, bimatoprost, latanoprost, or travoprost were applied to both eyes of animals of the respective groups for 1 week. At the end of treatment, ischemia was induced in both eyes of the 4 treatment groups by anterior chamber irrigation of the animals for 60 min. Following 24 h reperfusion, the animals were sacrificed. Enucleated eyes and retinal tissues were investigated by light microscopy, electron microscopy, immunohistochemicstry for retinal histopathology, intracellular and apoptotic cells and by retinal morphometry. Vitreous samples were biochemically investigated for probable role of reactive oxygen species, by measuring xanthine oxidase (XO) activity. Analysis of morphometric measurements and vitreous XO activity revealed significant differences between the PGA-treated groups and the NaCl-treated group (P<0.05). Similarly, apoptotic cell counts in different retinal layers showed that PGA-treated groups had fewer apoptotic cells in all retinal layers than the NaCl-treated ischemic group (P<0.05). PGA may have high protective potential for different retinal layers and cells. Biochemical analysis of vitreous showed that all PGAs decreased vitreous XO activity significantly compared to the NaCl-treated group (P<0.05). However we could not find any statistically significant differences among the analogues. PGAs may reduce the injury induced by I/R, through the inhibition of XO activity, and it seems that their effects are elicited through numerous pathways.

Topics: Amides; Animals; Antihypertensive Agents; Apoptosis; Bimatoprost; Cloprostenol; Disease Models, Animal; Latanoprost; Male; Neuroprotective Agents; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Rabbits; Reactive Oxygen Species; Reperfusion Injury; Retina; Retinal Diseases; Travoprost; Vitreous Body; Xanthine Oxidase

The formation of reactive oxygen species (ROS) may be important in the pathogenesis of microvascular dysfunction and injury in ischemic retinopathies. The authors hypothesized that retinal endothelial cells can generate injurious levels of superoxide radical in response to ischemia/reperfusion, that endothelial xanthine oxidase and cyclooxygenase are important enzymatic sources of superoxide radical under these conditions, and that superoxide scavengers and inhibitors of these enzymes can protect endothelium from ischemic injury. The authors used confluent cultures of mouse retinal endothelial cells (MREC) subjected to exogenously generated superoxide or simulated ischemia-reperfusion to test these hypotheses. Cell injury was assessed biochemically by lactate dehydrogenase release into the culture medium. MREC were injured in a duration-dependent fashion by exposure to the superoxide-generating mix of hypoxanthine and xanthine oxidase. Increasing periods of oxygen and glucose deprivation (OGD) for 5-9 hr followed by replenishment of substrates for 2 hr led to progressive increases in endothelial cell injury; a significant proportion of the injury occurred during the period of substrate replenishment. Significant MREC protection was achieved by the superoxide scavengers SOD (1000 U ml(-1)) and a carboxylic acid derivative of carboxyfullerene (10 microM), the xanthine oxidase inhibitors oxypurinol (100 microM) and diphenyleneiodonium (DPI) (100 n M), and the cyclooxygenase inhibitors indomethacin (300 microM) and ibuprofen (300 microM). It is concluded that MREC are vulnerable to auto-oxidative injury by superoxide radical generated following a period of OGD. Both xanthine oxidase- and cyclooxygenase-dependent pathways are important enzymatic sources of superoxide formation in this setting. These enzymes and the ROS produced from their activity may be viable therapeutic targets to reduce microvascular dysfunction and injury in ischemic retinopathies.

Topics: Animals; Cell Hypoxia; Cells, Cultured; Endothelium, Vascular; Female; Hypoxanthine; L-Lactate Dehydrogenase; Mice; Prostaglandin-Endoperoxide Synthases; Reperfusion Injury; Retinal Diseases; Retinal Vessels; Superoxide Dismutase; Superoxides; Xanthine Oxidase

We developed a quantitative histologic method for assessing injury in the rat retina due to transient ischemia. We used this technique to test the effectiveness of local hypothermia and allopurinol, an inhibitor of oxygen-free radical formation, in reducing ischemia/reperfusion injury in the rat retina. Retinal ischemia and reperfusion was produced by transient ligation of the optic nerve. Histologic evaluation by a masked observer was based on the average count of nonpyknotic nuclei in the inner nuclear layer of the retina from eight high power fields (X100) in one 5 microns thick sagital section at or near the optic nerve. A sharp increase in tissue damage occurs between 90 and 120 min of ischemia. Ischemia for periods of 60 and 90 min produced mild damage while periods of 120 and 240 min produced severe damage. Hypothermia protected the retina significantly from 120 min of ischemic injury (P less than 0.001 student t-test, compared to 120 min control), while allopurinol had no protective effect.

Topics: Allopurinol; Animals; Hypothermia, Induced; Rats; Rats, Inbred Strains; Reperfusion Injury; Retinal Diseases; Retinal Vessels; Time Factors