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Hannah Youngblood, Jingwen Cai, Hongfang Yu, Patricia Schoenlein, Daniel Stamer, Yutao Liu; Estrogen and Its Receptor ESR1 in Aqueous Humor and Trabecular Meshwork. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1000.
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Intraocular pressure (IOP) is the only modifiable risk factor for primary open-angle glaucoma (POAG). Several epidemiological studies have suggested that estrogen levels correlate negatively with IOP levels. We aimed to determine the presence of estrogen in aqueous humor (AH) and the potential role of estrogen and its receptor ESR1 (estrogen receptor 1) on trabecular meshwork cells.
First, to mimic the effects of IOP on TM, we subjected TM cell monolayers from healthy human donors (n=5) to 15% cyclical mechanical stretch (24 hours, 1 cycle/s) using a Flexcell Unit. Differentially expressed (DE) mRNAs and lncRNAs were identified by total RNA-sequencing followed by DESeq2 and a paired two-tailed student’s t-test respectively. Subsequently, pathway and gene ontology analyses were conducted on DE genes using WebGestalt while lncRNAs were analyzed for sequence similarity using NONCODE and NCBI BLASTn. Second, we tested the expression of Esr1 in primary bovine TM cells using qRT-PCR (n=3). Third, we measured the concentration of estradiol in AH samples taken from non-glaucoma human cataract patients (n=8), bovine eyes (n=10), and porcine eyes (n=8) using a 17β-estradiol ELISA kit from Enzo Life Sciences.
First, we identified 182 protein-coding mRNAs and 391 lncRNAs that were differentially expressed (|fold change| > 2, p < 0.05) in response to cyclic mechanical stretch. Several of the stretch-induced mRNAs in TM cells, such as CTGF, TXNIP, PTGDS, and HMOX1, were related to estradiol response. Furthermore, the steroid metabolism pathway was significantly enriched in our pathway analysis of these DE mRNAs, and one DE lncRNA shared sequence similarity with G protein-coupled estrogen receptor 1. Esr1 was expressed in bovine TM cells at a detectable level, and estradiol was present in human (54.6 ± 4.6pg/mL), bovine (57.3 ± 4.3pg/mL), and porcine (106.4 ± 42.5pg/mL) AH samples.
We have identified a potential role of estrogen and ESR1 in the mechanical response of TM cells to stretch. The presence of estradiol in aqueous humor and Esr1 expression in TM cells justifies the necessity of additional work in this area.
This is a 2020 ARVO Annual Meeting abstract.
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