Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States.
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.
Vision Res. 2024 Dec;225:108507. doi: 10.1016/j.visres.2024.108507. Epub 2024 Oct 30.
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.
最近有研究表明，更年期提前与青光眼的发病风险增加有关。在这里，我们研究了年龄和卵巢切除术（OVX）引起的人工绝经如何影响先前与青光眼相关的基因途径的基因表达，如细胞外基质（ECM）重塑和 TGF-β信号通路。我们使用 bulk RNA 测序分析了年轻（3-4 个月）和中年（9-10 个月）长耳大鼠的后极组织（巩膜和视神经头部），但也检查了视网膜，以比较不同组织区域的观察到的变化。我们的结果表明，衰老和 OVX 显著改变了巩膜和视神经头部的基因表达。一般来说，OVX 引发了免疫相关过程的富集。然而，年轻大鼠的 OVX 也导致 ECM 和 TGF-β基因集的显著富集。同时，这些影响在中年大鼠中减弱，表明 OVX 对基质相关途径的影响具有年龄依赖性。值得注意的是，在后眼和视网膜中，转录因子 Fos 在老年和 OVX 动物中下调。Fos 是细胞增殖和存活的主要调节剂，其失调可能在女性衰老和绝经中起重要作用。这些发现强调了绝经时间在调节与青光眼相关的分子途径中的重要作用，这与临床研究一致，表明早期绝经可能会增加患这种疾病的风险。这项研究还强调了考虑女性健康因素（如绝经）在理解和管理青光眼风险方面的重要性。
