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I. V. Glybina, A. Kennedy, J. A. Dykens, G. Abrams, R. Iezzi; Intravitreal Injections of Estradiol Preserve RCS Rat Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2197.
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© ARVO (1962-2015); The Authors (2016-present)
To determine neuroprotective effects of intravitreally injected estradiol analog in the RCS rat retinal degeneration model.
Twenty albino RCS rats were assigned as follows: 1) intravitreal injections of 0.05 µg estradiol analog (EA); 2) intravitreal injections of 0.005 µg EA; 3) DMSO-injected controls; 4) uninjected light-exposed controls. Bilateral intravitreal injections were performed at 5 and 7 weeks of age. Animals were followed by weekly electroretinogram (ERG) with initial ERG recorded immediately prior to the first injection. At 9 weeks, after four-week period, animals were sacrificed. One eye from each animal was used for histology and another eye was used for immunohistochemistry. Histological outer nuclear layer (ONL) and inner nuclear layer (INL) cell counts were performed upon three entire retinal sections for each eye within four eccentric areas on each side of the optic nerve. For immune-analysis, ED-1 antibody-labelled microglial cell processes were counted. Total microglial cell counts were made via IBA-1 immunohistochemical staining in retina wholemounts.
ERG a- and b-wave amplitudes in EA-treated groups were 15-25% higher than those in DMSO and uninjected controls (p<0.01). Histology analysis showed 27-44% preservation in ONL cell counts in EA-treated groups versus control groups (p<0.01). No difference was found within the INL cell counts between groups. Activated microglia cell counts in the EA-treated groups showed 2-2.5-fold reduction comparing to the controls (p<0.001). For all measured parameters, lower dose of EA showed better retinal preservation, however, no statistically significant difference was observed between the two EA-treated groups.
Intravitreal injections of EA are neuroprotective and modulate the cell-mediated immune response in RCS rat retinal degeneration. Our results show that EA could be a potentially useful treatment strategy for retinitis pigmentosa in humans.
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