# Targeting the PPAR-γ/OPTN axis to inhibit apoptosis in steroid-induced glaucoma

## TL;DR

This study explores how activating PPAR-γ and OPTN can reduce cell death in steroid-induced glaucoma, offering a potential treatment approach.

## Contribution

The study identifies the PPAR-γ/OPTN axis as a novel therapeutic target for steroid-induced glaucoma.

## Key findings

- PPAR-γ activation reduces apoptosis in trabecular meshwork cells.
- OPTN functions downstream of PPAR-γ to protect against glaucoma.
- Pioglitazone, a PPAR-γ activator, alleviates glaucoma in rat models.

## Abstract

Steroid-induced glaucoma (SIG) is the most common form of secondary glaucoma and is characterized by trabecular meshwork dysfunction and elevated intraocular pressure. Here, we investigated the contribution of trabecular meshwork cell (TMC) apoptosis to SIG pathogenesis using both in vivo and in vitro models. In a rat SIG model, reduced TMC density and increased apoptosis were observed. Integrated transcriptomic and proteomic analyses identified reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) expression in SIG TMCs, which was validated by immunohistochemistry and immunoblotting. Functional enhancement of PPAR-γ attenuated TMC apoptosis and suppressed the activation of the NF-κB/Bax/Bcl-2/caspase-3 signaling pathway. Mechanistically, optineurin (OPTN) was identified as a downstream target of PPAR-γ, with PPAR-γ directly binding to the OPTN promoter to regulate its transcription. Genetic disruption of OPTN diminished the protective effects of PPAR-γ. In vivo modulation of the PPAR-γ/OPTN axis alleviated trabecular meshwork injury, reduced apoptosis, and lowered intraocular pressure, highlighting a regulatory pathway linked to SIG progression.

•PPAR-γ activation suppresses trabecular meshwork cell apoptosis•OPTN acts downstream of PPAR-γ to protect against steroid-induced glaucoma•Pioglitazone alleviates steroid-induced glaucoma in rat models

PPAR-γ activation suppresses trabecular meshwork cell apoptosis

OPTN acts downstream of PPAR-γ to protect against steroid-induced glaucoma

Pioglitazone alleviates steroid-induced glaucoma in rat models

Natural sciences; Biological sciences; Molecular biology