TPM2 regulates contractility and biomechanical properties in trabecular meshwork cells

Area of Science:

• Ocular Biology
• Cellular Biomechanics
• Glaucoma Research

Background:

• Trabecular meshwork (TM) cell contraction-relaxation balance is crucial for regulating aqueous humor outflow resistance.
• Dysfunctional TM cell contractility, including hypercontractility and impaired relaxation, can obstruct outflow and reduce the effectiveness of glaucoma therapies.
• The molecular regulators of TM cell contractility are not fully understood, particularly in the context of primary open-angle glaucoma (POAG).

Purpose of the Study:

• To investigate the role of Tropomyosin 2 (TPM2) in regulating the contractility of human TM cells (HTMCs).
• To determine how TPM2 expression affects the expression of key contractile and cytoskeletal proteins within TM cells.
• To assess the impact of TPM2 modulation on the biomechanical properties of HTMCs.

Main Methods:

• Analysis of single-cell RNA sequencing data to identify abnormal tropomyosin family member (TPM) expression in POAG.
• Experimental modulation of TPM2 expression levels in HTMCs.
• Quantitative assessment of contractile-related molecular expression (ACTC1, TNNT2, α-SMA, F-actin).
• Measurement of cellular elastic modulus to evaluate biomechanical properties.

Main Results:

• Abnormal TPM expression patterns were observed in TM cell subpopulations of primates with POAG.
• Modulating TPM2 expression in HTMCs significantly altered the expression of ACTC1, TNNT2, α-SMA, and F-actin.
• Changes in TPM2 levels were associated with alterations in the cellular elastic modulus of HTMCs.

Conclusions:

• TPM2 plays a significant role in regulating TM cell contractility.
• TPM2 influences cytoskeletal architecture and biomechanical properties of TM cells.
• TPM2 may be a key regulator of aqueous humor outflow and a potential therapeutic target for glaucoma.