RNA-seq transcriptomic profiling of TGF-β2-exposed human trabecular meshwork explants: Advancing insights beyond...

Area of Science:

• Ophthalmology
• Molecular Biology
• Cell Biology

Background:

• Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss.
• Increased intraocular pressure (IOP) is a major risk factor for POAG.
• The trabecular meshwork (TM) regulates IOP by filtering aqueous humor.
• Transforming growth factor-beta 2 (TGF-β2) signaling is implicated in TM dysfunction in POAG.

Purpose of the Study:

• To investigate the transcriptomic and morphological effects of TGF-β2 on human TM explants.
• To elucidate the molecular mechanisms underlying TGF-β2-induced TM dysfunction relevant to POAG.

Main Methods:

• Utilized human TM explants to mimic in vivo conditions.
• Performed bulk RNA sequencing to analyze gene expression changes.
• Conducted immunohistological analysis to assess morphological alterations.

Main Results:

• TGF-β2 exposure led to significant upregulation of genes involved in extracellular matrix (ECM) regulation and fibrotic signaling.
• Morphological changes included cytoskeletal rearrangements and ECM deposition.
• Enrichment analysis revealed TGF-β2's influence on bone morphogenic protein (BMP) and Wnt signaling pathways.

Conclusions:

• TGF-β2 significantly alters TM cell biology, promoting fibrotic pathways.
• These transcriptomic and morphological changes provide insights into POAG pathophysiology.
• Understanding these pathways is crucial for developing novel therapeutic strategies targeting glaucoma.