Technological advances in ocular trabecular meshwork in vitro models for glaucoma research

Abstract

Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by the progressive degeneration of the optic nerve. Intraocular pressure (IOP), which is considered to be the main risk factor for glaucoma development, builds up in response to the resistance (resistance to what?) provided by the trabecular meshwork (TM) to aqueous humor (AH) outflow. Although the TM and its relationship to AH outflow have remained at the forefront of scientific interest, researchers remain uncertain regarding which mechanisms drive the deterioration of the TM. Current tissue‐engineering fabrication techniques have come up with promising approaches to successfully recreate the TM. Nonetheless, more accurate models are needed to understand the factors that make glaucoma arise. In this review, we provide a chronological evaluation of the technological milestones that have taken place in the field of glaucoma research, and we conduct a comprehensive comparison of available TM fabrication technologies. Additionally, we also discuss AH perfusion platforms, since they are essential for the validation of these scaffolds, as well as pressure–outflow relationship studies and the discovery of new IOP‐reduction therapies.

Nanofibrous PCL-Based Human Trabecular Meshwork for Aqueous Humor Outflow Studies

“…Hydrogels have also shown their suitability for HTMC behavioral studies, 16,17 especially in morphological and stiffness-related cues. 20,41,42 Electrospinning-based PCL scaffolds have also been used to imitate the three-layered graded porous HTM architecture. Despite the promising results, MEW requires specialized machines, and its scaffolds present limitations when creating small pores.…”

“…One of the main referent in HTM engineered models is the SU-8-based outflow platform, which has allowed perfusion studies with different drugs. − However, HTMC were not able to migrate into a 3D environment and were influenced by surface morphologies and stiffness. Hydrogels have also shown their suitability for HTMC behavioral studies, , especially in morphological and stiffness-related cues. ,, Electrospinning-based PCL scaffolds have also been used to imitate the three-layered graded porous HTM architecture. Despite the promising results, MEW requires specialized machines, and its scaffolds present limitations when creating small pores .…”

Chronic Glaucoma Induced in Rats by a Single Injection of Fibronectin-Loaded PLGA Microspheres: IOP-Dependent and IOP-Independent Neurodegeneration

“…In addition, males tend to have more fibrosis and females more connective tissue elasticity [ 62 ]. FN deposition in the trabecular meshwork matrix could increase stiffness and thus produce more resistance to aqueous humour outflow [ 63 , 64 ] and increase IOP. Males presented a tendency toward higher retinal thickness as measured by OCT in the retina and pRNFL protocols, but lower GCL thickness.…”

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model

“…In the eye, the ciliary body secretes AH, which circulates within the anterior chamber before draining from the eye through the TM 7 . In the conventional AH outflow pathway, the AH traverses the TM, initially passing through the uveal meshwork (UM) through the corneoscleral meshwork (CM) and finally to the juxtacanalicular tissue (JCT) before entering Schlemm's canal 35,36 (Fig. 1A-B).…”