Influence of sex on neuroretinal degeneration: 6 month follow-up in rats with chronic glaucoma

Abstract Purpose To evaluate differences by sex in the neuroretina of rats with chronic glaucoma (CG) induced by two different methods of increased ocular hypertension (OHT) vs healthy animals (HA). Methods Forty‐six Long Evans rats (18 males, 28 females) with CG and paired HA were analyzed. Glaucoma was achieved by sclerosing the episcleral veins or by injecting microspheres into the anterior chamber. Intraocular pressure was measured every week by Tonolab ® tonometer, neuroretinal function was recorded by dark/light‐adapted RETIanimal® electroretinography (ERG) at 0, 12 and 24 weeks; and structure was analyzed by Spectralis high definition Heidelberg ® optical coherence tomography (OCT), using the Retina, Retinal Nerve Fiber Layer (RNFL) and Ganglion Cell Layer (GCL) protocols at 0, 8, 12, 18 and 24 weeks. Results Males showed statistically significant higher IOP in both CG models and HA (p < 0.05). Greater differences were found in the episcleral model at early stages. Males with episclerally induced glaucoma showed higher increase (p < 0.05) in retinal thickness in OCT recordings than its females, microspheres model and HA. CG rats showed bigger thickness loss of RNFL and GCL (p < 0.05) comparing HA. Males showed a higher percentage of RNFL thickness loss (p < 0.05) in both models and HA. No differences by sex were observed in GCL thickness in the episcleral model, but comparison in microspheres model and HA showed differences. Males exhibited worse dark/light‐adapted functionality in CG models (p < 0.05), with worsened in the episcleral model at 12 weeks, than paired females and HA. Conclusions Male rats experienced higher IOP, structural loss and worse neurorretinal functionality than females under physiological and glaucomatous conditions. Sex and the OHT‐inducing method influenced neuroretinal degeneration.