Abstract
Purpose :
Recent works have shown that menopause is associated with the risk of glaucoma (Vajarant et al. 2016; Madjedi et al. 2022). Our preclinical work showed that surgical menopause via ovariectomy (OVX) led to lower visual function after retinal ganglion cell (RGC) injury (Feola et al., 2019; Allen et al. 2021). Exercise is a non-invasive and low-cost intervention that may preserve vision after RGC injury. We evaluated the benefit of voluntary exercise on visual outcomes after optic nerve crush (ONC) in female rats.
Methods :
To examine the benefit of exercise we divided Brown Norway (3-4 months, n=6 per cohort) rats into 1) non-operated female without exercise (Naïve inactive), 2) non-operated female with exercise (Naïve active), 3) OVX without exercise (OVX inactive), and 4) OVX with exercise (OVX active). Five weeks after the OVX surgery date, active cohorts were moved to a home cage connected to a running wheel to allow voluntary exercise. Eight weeks after OVX one eye experienced ONC while the contralateral eye was an internal control (CL). We assessed all animals at baseline and every 4 weeks for 12 weeks post-ONC for their spatial frequency threshold (visual acuity) using the optomotor response. We used two-way repeated measures ANOVAs to compare the cohorts between the eyes (ONC vs. CL) and across time (p<0.05) with appropriate post hoc tests.
Results :
At 12 weeks post-injury (Figure), ONC caused a significant decline in visual acuity in the Naïve inactive (p=0.017), OVX inactive (p<0.0001), and OVX active (p=0.013) compared to CL eyes. We found that the OVX inactive cohort had the lowest visual acuity (p<0.0001) compared to the Naïve inactive cohort after ONC. However, we observed that exercise tended to improve visual acuity after ONC in all cohorts. There was a 7% higher visual acuity (p<0.03) in Naïve active females and 17% highest visual acuity (p<0.0001) in OVX active females compared to their respective inactive controls.
Conclusions :
Overall, ONC decreased visual function at 12 weeks, but visual function was lowest in the inactive OVX cohort. We found improved visual function in all active cohorts, with active OVX animals having the largest benefit of exercise. These data suggest that exercise offers a potential therapy for preventing visual deficits after RGC injury. Future work will evaluate retinal function and structural changes and the underlying mechanisms.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.