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MS Ola, P Moore, DM Maddox, A EL-Sherbeny, N Agarwal, V Ganapathy, SB Smith; Sigma Receptor (R1) is Expressed in Retinal Ganglion Cells (RGC) Under Normal and Diabetic Conditions . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1326.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: σR1 are nonopiate, nonphencyclidine binding sites that mediate the psychotomimetic actions of certain opioid derivatives. They mediate pharmacological and physiological functions including neuroprotection against overstimulation of the NMDA receptor. We demonstrated recently that σR1 is expressed in RGCs. RGCs are known to undergo apoptosis early in diabetic retinopathy via NMDA receptor overstimulation. In this study, we asked whether RGCs cultured under hyperglycemic conditions and RGCs of diabetic mice express σR1. Methods: RGCs were cultured 48 h in medium containing either 45 mM glucose or 11 mM glucose plus 34 mM mannitol (osmolar control). Cells were subjected to semiquantitative RT-PCR to determine mRNA levels encoding σR1. In addition, mRNA encoding σR1 was examined in neural retinas of streptozotocin-induced diabetic mice at 3, 6 and 12 weeks post-onset of diabetes. In situ hybridization (ISH) was done to determine specifically whether ganglion cells of diabetic mice express σR1 mRNA. Immunohistochemical (IMH) analysis of σR1 was performed in intact retinas of normal and diabetic mice 2, 6 and 12 weeks post-onset of diabetes. Results: RT-PCR analysis of cultured RGCs showed that σR1 mRNA is expressed under hyperglycemic conditions at levels similar to control cells. RT-PCR analysis of retinas of diabetic mice showed no difference at 3 and 6 weeks in levels of mRNA encoding σR1 compared to retinas of control mice. ISH and IMH of σR1 mRNA and protein, respectively, were similar between diabetic and control mice. Conclusions: σR1 is expressed in RGCs under hyperglycemic conditions in vitro and in vivo. These data suggest that σR1 ligands might offer neuroprotection of RGC loss in diabetic retinopathy.
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