TGF-{beta}2 induces senescence-associated changes in human trabecular meshwork cells.

Area of Science:

• Ophthalmology
• Cell Biology
• Molecular Biology

Background:

• Cellular senescence is implicated in primary open-angle glaucoma (POAG) pathogenesis.
• Transforming growth factor-β2 (TGF-β2) is a key mediator in the pathological changes of the trabecular meshwork (TM) in POAG.

Purpose of the Study:

• To investigate whether TGF-β2 induces senescence-associated changes in human TM cells in vitro.
• To explore the role of TGF-β2 in TM cell aging relevant to POAG.

Main Methods:

• Human TM cells were treated with TGF-β2.
• Assessed senescence markers: SA-β-Gal activity, lipid peroxidation, and mRNA expression of Apo J, SM22, SPARC.
• Examined the effects of antioxidants and analyzed senescence-related signaling pathways (p16, p21, pRb).

Main Results:

• TGF-β2 exposure increased SA-β-Gal activity, lipid peroxidation, and expression of Apo J, SM22, and SPARC mRNA.
• These TGF-β2-induced changes were reduced by antioxidants.
• TGF-β2 upregulated p16 expression and downregulated pRb protein, indicating activation of the p16-pRb pathway.

Conclusions:

• TGF-β2 triggers senescence-associated alterations in human TM cells in vitro.
• TGF-β2 activates the p16-pRb signaling pathway, contributing to TM cell aging.
• Reducing TGF-β2 levels may offer a therapeutic strategy to prevent TM aging in POAG.