Human trabecular meshwork cells express BMP antagonist mRNAs and proteins

Area of Science:

• Ophthalmology
• Cell Biology
• Biochemistry

Background:

• Glaucoma is associated with elevated transforming growth factor-beta2 (TGF-β2) levels in aqueous humor and trabecular meshwork (TM).
• TGF-β2 promotes extracellular matrix (ECM) deposition in the TM, increasing resistance to aqueous humor outflow.
• Bone morphogenetic protein (BMP) 4 counteracts TGF-β2's profibrotic effects, a process reversed by the BMP antagonist gremlin, indicating opposing roles of BMP and TGF-β signaling.

Purpose of the Study:

• To investigate the expression of additional BMP antagonists (noggin, chordin, BMPER, BAMBI, Smurf1/2) in cultured human TM cells.
• To determine if exogenous TGF-β2 treatment regulates the expression of these BMP antagonists in human TM cells.

Main Methods:

• Primary human TM cells were cultured and treated with TGF-β2 (5 ng/ml) for 24 or 48 hours.
• Quantitative PCR (qPCR) was used to assess mRNA levels.
• Western immunoblots (WB) were employed to evaluate protein expression.

Main Results:

• Human TM cells express mRNAs and proteins for noggin, chordin, BMPER, BAMBI, and Smurf1/2.
• TGF-β2 treatment decreased chordin, BMPER, BAMBI, and Smurf1 mRNA and protein levels.
• Conversely, TGF-β2 increased secreted noggin and Smurf2 mRNA and protein levels.

Conclusions:

• BMP antagonist members are expressed in the human TM.
• These antagonists may play roles in normal TM function and pathogenesis.
• Altered expression of BMP antagonists could lead to functional changes in the human TM, potentially impacting glaucoma development.