# Characterizing the expression profile of Dexras1 in human trabecular meshwork cells

## TL;DR

This study explores how dexamethasone affects Dexras1 expression in human trabecular meshwork cells, potentially linking it to steroid-induced glaucoma.

## Contribution

The study reveals an age-dependent response of Dexras1 to dexamethasone, offering a new perspective on steroid-induced glaucoma.

## Key findings

- Dexamethasone significantly upregulates Dexras1 in trabecular meshwork cells within 30 minutes to 1 hour.
- Dexras1 induction varies by donor age, with younger and older donors showing significant upregulation but middle-aged donors showing little change.
- The age-dependent response of Dexras1 may explain the higher prevalence of steroid-induced glaucoma in younger and older populations.

## Abstract

Corticosteroids are a mainstay therapy for the treatment of ocular and systemic inflammatory conditions but are associated with a significant risk of intraocular pressure elevation, or ocular hypertension. If intraocular pressure is inadequately controlled, steroid-induced glaucoma may develop, which can result in permanent vision loss and irreversible blindness. Pathological changes akin to fibrosis in the trabecular meshwork, the tissue responsible for intraocular pressure regulation, have been well described and contribute to the development of steroid-induced ocular hypertension and glaucoma. However, the molecular mechanisms driving these fibrosis-like changes in the trabecular meshwork following steroid treatment remain poorly understood. RASD1 is a gene coding for Dexras1, a small G protein of the Ras family discovered based on its marked induction by the synthetic glucocorticoid dexamethasone. Accumulating evidence points to the role of glucocorticoids in alterations of trabecular meshwork cell morphology, growth, and cell-extracellular matrix interactions. Therefore, we sought to confirm and further characterize how glucocorticoid-induced Dexras1 expression may contribute to glaucoma pathology in vitro. In this study, we found that dexamethasone significantly upregulated the expression of Dexras1 in trabecular meshwork cells within 30 min to 1 h post treatment. In addition, we discovered two phenotypes of Dexras1 induction independent of glucocorticoid responsiveness: younger and older donors show significant upregulation of Dexras1, whereas middle-aged donors experience little to no changes in Dexras1 expression after dexamethasone treatment. This age-dependent Dexras1 response may provide a novel explanation for the greater prevalence of steroid-induced glaucoma observed in older and younger populations as opposed to middle-aged populations.

•Steroid glaucoma is related to pathologic changes in the trabecular meshwork.•Dexras1 is a protein induced in tissues in response to dexamethasone (dex).•We examined Dexras1 expression in nine human trabecular meshwork cell strains.•Dex results in time-dependent upregulation of Dexras1 in trabecular meshwork cells.•We theorize that Dexras1-induced adipogenesis contributes to steroid glaucoma.

Steroid glaucoma is related to pathologic changes in the trabecular meshwork.

Dexras1 is a protein induced in tissues in response to dexamethasone (dex).

We examined Dexras1 expression in nine human trabecular meshwork cell strains.

Dex results in time-dependent upregulation of Dexras1 in trabecular meshwork cells.

We theorize that Dexras1-induced adipogenesis contributes to steroid glaucoma.