Abstract
Glaucoma is a group of optic neuropathies characterized by the progressive degeneration of retinal ganglion cells (RGCs). Patients with glaucoma generally experience elevations in intraocular pressure (IOP), followed by RGC death, peripheral vision loss and eventually blindness. However, despite the substantial economic and health-related impact of glaucoma-related morbidity worldwide, the surgical and pharmacological management of glaucoma is still limited to maintaining IOP within a normal range. This is in large part because the underlying molecular and biophysical mechanisms by which glaucomatous changes occur are still unclear. In the present review article, we describe current tissue-engineered models of the intraocular space that aim to advance the state of glaucoma research. Specifically, we critically evaluate and compare both 2D and 3D-culture models of the trabecular meshwork and nerve fiber layer, both of which are key players in glaucoma pathophysiology. Finally, we point out the need for novel organ-on-a-chip models of glaucoma that functionally integrate currently available 3D models of the retina and the trabecular outflow pathway.
Highlights
Glaucomas are a heterogeneous group of optic neuropathies characterized by the progressive degeneration of retinal ganglion cells (RGCs) [1]
We compare current tissue engineered models of aqueous humor (AH) outflow and RGC degeneration, highlighting those which mobilize soft lithography, electrospinning, microfluidics, hydrogel 3D scaffolds and 3D bioprinting technologies. Integrating this information, we propose a novel, three-dimensional (3D) organ-on-a-chip model of glaucomatous physiology that combines currently available models of both trabecular outflow and RGC degeneration. We argue that this platform will help us better understand how intraocular pressure (IOP) contributes to RGC degeneration during glaucoma progression
We summarized and compared the 2D and 3D tissue engineered models of glaucoma currently being used in ophthalmic research and regenerative medicine
Summary
Glaucomas are a heterogeneous group of optic neuropathies characterized by the progressive degeneration of retinal ganglion cells (RGCs) [1]. A better understanding of the molecular details associated with RGC damage and how these details differ between individual glaucoma patients, will inform the development of more targeted, patient-specific cell therapies This all highlights the need for tissue engineered models of glaucomatous physiology that more closely recapitulate the AH outflow pathways and RGC degeneration observed in vivo. We compare current tissue engineered models of AH outflow and RGC degeneration, highlighting those which mobilize soft lithography, electrospinning, microfluidics, hydrogel 3D scaffolds and 3D bioprinting technologies Integrating this information, we propose a novel, three-dimensional (3D) organ-on-a-chip model of glaucomatous physiology that combines currently available models of both trabecular outflow and RGC degeneration. We argue that this platform will help us better understand how IOP contributes to RGC degeneration during glaucoma progression. We describe how our proposed model better recapitulates the in vivo cell–cell and cell-extracellular matrix (ECM) interactions that mediate glaucoma-related vision loss
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