Ovariectomy Drives Increase an ECM Transcription Signature in the Posterior Eye and Retina
The risk of developing glaucoma has recently been associated with the age of menopause. This study examines how age and surgical menopause via ovariectomy (OVX) impact gene expression in the posterior eye, including the sclera and optic nerve head. We examined how age and OVX impacted expression pathways linked to glaucoma, such as extracellular matrix (ECM) remodeling and TGF-ß signaling. To compare these changes across different tissue regions, we also examined the retina. Using bulk RNA sequencing, we analyzed these changes in young (3-4 months) and middle-aged (9-10 months) Long-Evans rats. Our results demonstrate that both aging and OVX significantly alter gene expression in these ocular tissues. Specifically, OVX in young rats led to significant enrichment of ECM and TGF-ß gene sets, while these effects were diminished in middle-aged rats, indicating an age-dependent influence. Early OVX triggered significantly enriched ECM remodeling and immune responses compared to later OVX. These findings underscore the critical role of menopause timing in modulating molecular pathways associated with glaucoma, suggesting that early menopause may heighten the risk of developing this condition. Notably, FOS was downregulated in the posterior eye and retina in aging and OVX animals. FOS is a major regulator of cell proliferation and survival, and its dysregulation may play an important role in aging and menopause for women. This study highlights the importance of considering women's health factors, such as menopause, in understanding and managing glaucoma risk. Overall design: young (3-4 months old, n=12) and middle-aged (9-10 months old, n=12) Long-Evans rats.  Each group was subdivided, with some animals undergoing surgical menopause via ovariectomy  (n=6) and the remaining animals undergoing a Sham surgery (n=6).