Menopause‐induced neurodegeneration of retinal ganglion cells in a model of an acute retinal ischemia in rats

Abstract

Aims/Purpose: To assess the influence of surgical menopause on the function and survival of retinal ganglion cells in a rat model of optic nerve crush.Methods: A total of 27 rats, aged 8 weeks, were divided into two groups based on the duration between ovariectomy (OVE) and euthanasia. Subgroups consisted of OVE, OVE combined with optic nerve crush (ONC), and ONC alone. All surgical procedures were conducted under general anaesthesia. Menopause was induced through OVE, which involved the surgical removal of ovaries. ONC was performed to induce acute retinal ischemia. Retinal function was evaluated using electroretinography (ERG). Retinas were stained for β3‐tubulin, NeuN, Erα, Erβ, and Iba1. Cell loss ratios were assessed through manual counting using ImageJ software.Results: After a two‐week menopause period, a reduction in retinal interneurons (RI) density was observed, but no significant decline was observed in retinal ganglion cell (RGC) count. The counts for NeuN were 373 ± 58 and 317 ± 55 (healthy vs. OVE, p < 0.02), and for β3‐tubulin were 197 ± 42 and 212 ± 38 (healthy vs. OVE, p > 0.05), respectively. Seven weeks after OVE, menopause affected RI but not RGC, with counts of 404 ± 49 and 378 ± 61 (healthy vs. OVE, p < 0.05), and 286 ± 32 and 287 ± 51 (healthy vs. OVE, p > 0.05) for NeuN and β3‐tubulin, respectively. Following the ONC procedure, the NeuN cell count was 345 ± 28 and 286 ± 40 (ONC and ONC + OVE, respectively, p < 0.0001), and for β3‐tubulin it was 221 ± 28 and 200 ± 37 (ONC and ONC + OVE, respectively, p < 0.05). In the preliminary analysis of ERG, a significant decrease in PhNR amplitudes was observed in the OVE group, while PhNR was severely diminished in the OVE + ONC group.Conclusions: Deprivation of estrogens through surgical menopause leads to accelerated retinal neurodegeneration, primarily affecting retinal interneurons. The absence of estrogens increases the vulnerability of RGCs to insults, resulting in expedited RGC loss during acute retinal ischemia.