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JM Kwong, Y-W Lan, Y Ishii, J Caprioli; Pretreatment of 2-deoxy-D-glucose Protects Retinal Neurons Against N-methyl-D-aspartate-induced Cell Death in Adult Rat . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2194.
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Purpose: 2-deoxy-D-glucose (2DG), a non-metabolizable analog of glucose, is used to reduce glucose availability to cells to mimic food restriction. This study is to evaluate the protective effect of 2DG against N-methyl-D-aspartate (NMDA)-induced cell loss in adult rat retinas and to examine the expression of heat shock protein (HSP) 70 family. Methods: Forty-four 45 to 50-day-old male Sprague Dawley rats were given daily intraperitoneal injections of 2DG (200mg/kg in saline) or vehicle for 7 days. Intravitreal injection of 2µ L 4mM NMDA solution or 0.1M PBS was given at 1 day after treatment of 2DG. At 7 days after NMDA injection, animals were euthanized and the enucleated eyeballs were bisected. Flat preparation of temporal retinas was performed and number of cresyl violet stained cells in the retinal ganglion cell layer (RGCL) was counted at central, mid-peripheral and peripheral retinas. The nasal half was processed for immunohistochemistry with antibodies against HSC70, HSP72, GRP75 and GRP78. Immunoreactivity (IR) was evaluated by counting the number of positive cells in the RGCL and grading the density of their labeling. Results: There was no remarkable weight loss after 7-day-administration of 2DG. At 7 days after NMDA injection, cell loss in the RGCL at all areas (52%, 42%, 36%) was significantly ameliorated by pretreatment of 2DG (16%, 17%, 14%). Positive labeling of HSP72, HSC70, GRP75 and GRP78 was shown in the RGCL of control retinas but the number of all HSPs labeled cells in the RGCL was reduced at 7 days after NMDA injection. However, sustained elevated labeling of HSP72 was detected in 2DG-treated control while increased IR of GRP78 was noted in NMDA-injected retinas with pretreatment of 2DG. No noticeable change in IR of HSC70 or GRP75 was detected after administration of 2DG. Conclusion: We found a neuroprotective effect of 2DG by increasing HSP72 and GRP78 in NMDA-induced cell loss in rat retinas. Food restriction-mediated stress response may protect retinal neurons against excitotoxicity
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