Targeting the PPAR-γ/OPTN axis to inhibit apoptosis in steroid-induced glaucoma
Xin Liang, Ning Li, Qiaoyun Gong, Haiyan Wang
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.
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…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsPeroxisome Proliferator-Activated Receptors · Glaucoma and retinal disorders · Protein Kinase Regulation and GTPase Signaling