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Characterizing the expression profile of Dexras1 in human trabecular meshwork cells
ChihWei Chen1,2, Jiapeng Han1,3, Luis Sanchez1,4
1Department of Ophthalmology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA.
Biochemistry and Biophysics Reports
|June 23, 2025
Summary
Corticosteroids can cause glaucoma by increasing intraocular pressure. This study shows the gene Dexras1 is upregulated by steroids in trabecular meshwork cells, particularly in younger and older individuals, potentially explaining age-related glaucoma risk.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Corticosteroids treat inflammatory conditions but risk elevated intraocular pressure (ocular hypertension), potentially causing steroid-induced glaucoma and vision loss.
- Fibrosis-like changes in the trabecular meshwork contribute to steroid-induced ocular hypertension, but underlying molecular mechanisms are unclear.
- The gene *RASD1* encodes Dexras1, a protein induced by the synthetic glucocorticoid dexamethasone, and glucocorticoids affect trabecular meshwork cell behavior.
Purpose of the Study:
- To investigate the role of glucocorticoid-induced Dexras1 expression in the pathogenesis of steroid-induced glaucoma *in vitro*.
- To characterize the temporal and age-dependent regulation of Dexras1 in trabecular meshwork cells following dexamethasone treatment.
Main Methods:
- Primary human trabecular meshwork cells from donors of varying ages were treated with dexamethasone.
- Quantitative analysis of Dexras1 gene expression was performed at different time points post-treatment.
Main Results:
- Dexamethasone significantly upregulated Dexras1 expression in trabecular meshwork cells within 30 minutes to 1 hour.
- Dexras1 upregulation showed distinct age-dependent phenotypes: significant induction in younger and older donors, but minimal change in middle-aged donors.
- These findings suggest an age-dependent Dexras1 response to glucocorticoids.
Conclusions:
- Glucocorticoid-induced Dexras1 expression in trabecular meshwork cells may contribute to steroid-induced glaucoma.
- The age-dependent regulation of Dexras1 offers a potential explanation for the higher prevalence of steroid-induced glaucoma in younger and older individuals compared to middle-aged ones.
- Targeting Dexras1 may offer a novel therapeutic strategy for preventing or treating steroid-induced glaucoma.
