Influence of Sex on Neuroretinal Degeneration: Six-Month Follow-Up in Rats With Chronic Glaucoma

Abstract

Purpose To evaluate differences by sex in the neuroretina of rats with chronic glaucoma over 24 weeks of follow-up, and to assess by sex the influence on neurodegeneration of different methods of inducing ocular hypertension. Methods Forty-six Long–Evans rats—18 males and 28 females—with induced chronic glaucoma were analyzed. Glaucoma was achieved via 2 models: repeatedly sclerosing the episcleral veins (9 male/14 female) or by injecting poly(lactic-co-glycolic acid) microspheres measuring 20 to 10 µm (Ms20/10) into the anterior chamber (9 male/14 female). The IOP was measured weekly by tonometer; neuroretinal function was recorded by dark/light-adapted electroretinography at baseline and weeks 12 and 24; and structure was analyzed by optical coherence tomography using the retina posterior pole, retinal nerve fiber layer and ganglion cell layer protocols at baseline and weeks 8, 12, 18, and 24. Results Males showed statistically significant ( P < 0.05) higher IOP in both chronic glaucoma models, and greater differences were found in the episcleral model at earlier stages. Males with episclerally induced glaucoma showed a statistically higher increase in retinal thickness in optical coherence tomography recordings than females and also when comparing Ms20/10 at 12 weeks. Males showed a higher percentage of retinal nerve fiber layer thickness loss in both models. Ganglion cell layer thickness loss was only detected in the Ms20/10 model. Males exhibited worse dark/light-adapted functionality in chronic glaucoma models, which worsened in the episcleral sclerosis model at 12 weeks, than females. Conclusions Female rats with chronic glaucoma experienced lower IOP and structural loss and better neuroretinal functionality than males. Sex and the ocular hypertension–inducing method influenced neuroretinal degeneration.

Multi-loaded PLGA microspheres as neuroretinal therapy in a chronic glaucoma animal model

“…In all cohorts in our study, males tended to have higher IOP values. This is consistent with the higher IOP levels found in male rats [59] and human males [60]. However, in the cohort treated with the neuroprotective formulation, no significant sex differences were found, suggesting that the proposed neuroprotective multiloaded formulation could be useful in both sexes.…”

Analysis of Parainflammation in Chronic Glaucoma Using Vitreous-OCT Imaging

“…In contrast, immune disturbances tend to be more frequent in females, but more severe in males [ 87 , 88 , 89 ]. Females have demonstrated an enhanced ability to control infection [ 86 ] and less neuroretinal tissue loss in the presence of glaucomatous noxa [ 90 ]. The greater vitreous intensity observed in females in the glaucoma models, as well as in healthy animals at later ages (28 weeks of age), suggests a greater immunogenic presence that could act in an initially reparative manner in the presence of hypertensive noxa or age-associated neoepitopes, maintaining retinal structure and function [ 62 , 90 ].…”

“…Females have demonstrated an enhanced ability to control infection [ 86 ] and less neuroretinal tissue loss in the presence of glaucomatous noxa [ 90 ]. The greater vitreous intensity observed in females in the glaucoma models, as well as in healthy animals at later ages (28 weeks of age), suggests a greater immunogenic presence that could act in an initially reparative manner in the presence of hypertensive noxa or age-associated neoepitopes, maintaining retinal structure and function [ 62 , 90 ]. These results highlight the importance of considering the influence of sex (traditionally not taken into account) and age in immune research, due to susceptibility to infectious, inflammatory or age-associated diseases such as glaucoma.…”

Proteomics-Based Identification of Retinal Protein Networks Impacted by Elevated Intraocular Pressure in the Hypertonic Saline Injection Model of Experimental Glaucoma

“…In addition, the hypertonic saline injection method to produce OHT by aqueous outflow obstruction has demonstrated strengths in replicating human glaucoma over alternative paradigms such as episcleral vein cauterization [ 29 , 43 ]. The use of males for the studies initially is also justified because glaucomatous male rats experience higher structural loss and display worse neuroretinal functionality than females [ 44 ].…”