Monosialoganglioside GM1 reduces ischemia-reperfusion induced injury in the rat retina. Invest Ophthalmol

Abstract

Purpose. Gangliosides are normal components of cell membranes, contribute to structural rigidity and membrane function, and have been shown to protect against various insults to the brain. This study evaluates the effect of exogenously administered monosialoganglioside GM1 on retinal damage induced by transient retinal ischemia and reperfusion. Methods. Retinal ischemia was induced unilaterally in Long Evans rats by increasing intraocular pressure to 160 mm Hg for 60 minutes. GM1 (30 mg/kg, intraperitoneally) or buffer controls were administered at 48 hours, 24 hours, and 15 minutes before ischemia, and survival time after ischemia was either 8 or 15 days. The degree of retinal damage was assessed by histopathologic study according to Hughes' quantification of ischemic damage. Results. Retinal ischemia led to significant reductions in thickness and cell number, principally in the inner retinal layers (30% to 80%), and to a lesser extent in the outer retinal layers (18% to 42%). Pretreatment with intraperitonealy injected monosialoganglioside GM1 conferred significant protection against retinal ischemic damage either 8 or 15 days after ischemic survival time. After 8 days reperfusion, the ischemic-induced loss in overall retinal thickness was reduced by 70%, and those of the inner nuclear and plexiform layers were reduced by 77% and 44%, respectively. Ischemic-induced ganglion cell, inner nuclear, and outer nuclear layer cell density losses were reduced by 45%, 40%, and 57%, respectively. After 15 days of reperfusion, approximately the same statistically significant differences could be observed in comparison with the 15-day ischemic-reperfusion group. Conclusions. Monosialoganglioside GM1 protects the rat retina from pressure-induced ischemic injury when administered intraperitonealy 2 days before insult. This protection afforded by GM1 can be observed even after 8 days or 15 days of reperfusion. Invest Ophthalmol Vis Sci. 1996; 37:267-273. VFangliosides are naturally occuring glycosphingolipids that contain one or more sialic acids and are particularly abundant in neuronal membranes.' They influence functional dynamics of the cellular membranes on several ways: They contribute to the structural rigidity of the membranes; they are involved in the transfer of information between neighboring cells or between cell surfaces and the extracellular environment (neurotransmitters, hormones); and they modulate cell growth by regulating proliferation and maturation processes controlled by polypeptide growth fac