Ovariectomy drives increase of an ECM transcription signature in the posterior eye and retina

Cydney A Wong; Gabriela Sanchez-Rodriguez; C Ross Ethier; Levi B Wood; Andrew J Feola

doi:10.1016/j.visres.2024.108507

Ovariectomy drives increase of an ECM transcription signature in the posterior eye and retina

Vision Res. 2024 Oct 29:225:108507. doi: 10.1016/j.visres.2024.108507. Online ahead of print.

Authors

Cydney A Wong¹, Gabriela Sanchez-Rodriguez², C Ross Ethier³, Levi B Wood⁴, Andrew J Feola⁵

Affiliations

¹ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States.
² Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States; Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, United States; Department of Ophthalmology, Emory University, Atlanta, GA, United States.
³ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States; Department of Ophthalmology, Emory University, Atlanta, GA, United States; George W. Woodruff School of Mechanical Engineering and Paker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, United States.
⁴ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States; George W. Woodruff School of Mechanical Engineering and Paker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, United States.
⁵ Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States; Department of Ophthalmology, Emory University, Atlanta, GA, United States; Center for Visual and Neurocognitive Rehabilitation, Joseph Maxwell Cleland Atlanta VA Medical Center, Atlanta, GA, United States. Electronic address: [email protected].

PMID: 39476526
DOI: 10.1016/j.visres.2024.108507

Abstract

Increased risk of developing glaucoma has recently been associated with early age of menopause. Here, we examined how age and surgically-induced menopause via ovariectomy (OVX) impacted gene expression in gene pathways previously linked to glaucoma, such as extracellular matrix (ECM) remodeling and TGF-β signaling. Using bulk RNA sequencing, we analyzed changes in young (3-4 months) and middle-aged (9-10 months) Long-Evans rats. We focused on posterior pole tissues (sclera and optic nerve head) but also examined the retina to compare observed changes across different tissue regions. Our results demonstrated that aging and OVX significantly alter gene expression in the sclera and optic nerve head. Generally, OVX triggered the enrichment of immune-related processes. However, OVX in young rats also led to significant enrichment of ECM and TGF-β gene sets. At the same time, these effects were diminished in middle-aged rats, indicating an age dependency of the effects of OVX on matrix-related pathways. Notably, the transcriptional factor Fos was downregulated in the posterior eye and retina in aged 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. These findings underscore the important role of menopause timing in modulating molecular pathways associated with glaucoma, which is consistent with clinical studies showing that early menopause may heighten the risk of developing this condition. This study also highlights the importance of considering women's health factors, such as menopause, in understanding and managing glaucoma risk.

Keywords: Aging; Glaucoma; Menopause; RNA sequencing.