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Abstract #45642 Published in IGR 13-2
Functional and morphological effects of (beta)-estradiol in eyes with N-methyl-d-Aspartate-induced retinal neurotoxicity in rats
Yamashita H; Yamada-Nakayama C; Sugihara K; Tsuji S; Sakurai T; Ban Y; Tsutsumi S; Sato YExperimental Eye Research 2011;
Glutamate-mediated excitotoxicity, mainly induced by N-methyl-d-aspartate (NMDA) receptors, is known to cause retinal ganglion cell death in retinal ischemia, glaucoma, and several other retinal diseases. We evaluated the effects of (beta)-estradiol (E2) against a single intravitreal injection of NMDA using a functional and morphological approach. Male rats were randomly divided into 3 treatment groups: (1) Control; (2) NMDA (intravitreal injection of 5 mM NMDA); and (3) NMDA + E2 (intravitreal injection of 5 mM NMDA and pretreatment with subcutaneous E2 implantation). Seven days after NMDA injection, full-field electroretinograms (ERGs) and quantitative morphological analyses using transverse sections of the retina were conducted. In the NMDA group, full-field ERGs showed reductions in the amplitudes of the negative-scotopic threshold response, rod response b-wave, oscillatory potentials, flicker response second b-wave and cone response b-wave. Morphological evaluations of transverse sections of the retina demonstrated a reduction in the thickness of the inner plexiform layer, increases in the thickness of the outer plexiform and outer nuclear layers, and a loss of cells in the ganglion cell layer. In the NMDA + E2 group, pretreatment with E2 prevented the aggravations in the amplitudes of the ERGs except for oscillatory potential 2 (OP2); however, no morphological differences between the NMDA and NMDA + E2 groups were seen. These findings indicate that E2 can protect retinal function against NMDA-induced neurotoxicity. In addition, these indications suggested that the effect of E2 may have therapeutic benefits in NMDA related diseases, such as retinal ischemia and glaucoma.
H. Yamashita. Drug Safety Laboratory, Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Lt, . Email: h.yamashita@po.rd.taisho.co.jp
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
11.8 Neuroprotection (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
