Photoinduced Gelatin-Methacrylate Scaffolds to Examine the Impact of Extracellular Environment on Trabecular Meshwork Cells

Glaucoma is the leading cause of irreversible blindness in the world, currently impacting 80 million people. Patients suffering from primary open-angle glaucoma experience aqueous humor accumulation within the eye causing an increase in intraocular pressure (IOP). The main cause of this rise in IOP is due to poor outflow of aqueous humor through the trabecular meshwork (TM), a tissue composed of collagen and glycosamino-glycans (GAGs) embedded with TM cells. The behavior of TM cells is impacted by their microenvironment, and studies conducted on two-dimensional plastic substrates do not necessarily reflect how TM cells would behave in their native setting. Here, we cultured human TM (hTM) cells on 3D biocompatible hydrogels composed of gelatin methacrylate (GelMA) incorporated with the glycosaminoglycans (GAGs) chondroitin sulfate (CS) and hyaluronic acid (HA). Mechanical properties were quantified by storage moduli and viscosity data. Cellular response was measured by quantifying cellular proliferation and expression of an important extracellular matrix protein, fibronectin. We have shown substrate mechanical properties to impact hTM cell proliferation over 2 weeks. It was found that the incorporation of GAGs impacted cell proliferation and fibronectin expression in hTM cells. This work will help elucidate hTM cell response with changes in their microenvironment.