Implementation of gelatin-methacrylate scaffolds for in vitro modeling of the trabecular meshwork

Abstract

Glaucoma is the leading cause of irreversible blindness in the world currently impacting 66.8 million people. There are several different types of Glaucoma with the most common one being primary open-angle glaucoma (POAG). Patients suffering from POAG experience aqueous humor accumulation within the eye causing an increase of pressure called the Intraocular Pressure (IOP). The cause of this rise of IOP is due to poor outflow of aqueous humor through the trabecular meshwork (TM). The TM is a 3D matrix composed of collagen and glycosaminoglycans (GAGs) embedded with endothelial-like TM cells. TM cells physiology is impacted by the morphology of the environment they are cultured in. This causes TM cells to behave differently in vitro compared to in vivo. This lack of function makes it difficult to screen novel drugs accurately. The goal of this research was to create a 3D hydrogel model to more accurately mimic the native TM. The first step was to develop and test a procedure to produce GelMA and fabricate it into scaffolds. The second step was to determine the optimal underlying GelMA concentration to use and to test the mechanical strength and swelling capabilities of these scaffolds in the presence of GAGs. The final step was to seed TM cells onto the various GelMA scaffolds and study the effect each scaffold, in the presence of dexamethasone (Dex), had on proliferation, gene expression, and cell morphology. The result of which produced several different GelMA scaffolds, each shown to influence TM cells in unique ways.