Retinal Tissue Bioengineering, Materials and Methods for the Treatment of Glaucoma

Abstract

Background: Glaucoma, a characteristic type of optic nerve degeneration in the posterior pole of the eye, is a common cause of irreversible vision loss and the second leading cause of blindness worldwide. As an optic neuropathy, glaucoma is identified by increasing degeneration of retinal ganglion cells (RGCs), with consequential vision loss. Current treatments only postpone the development of retinal degeneration, and there are as yet no treatments available for this disability. Recent studies have shown that replacing lost or damaged RGCs with healthy RGCs or RGC precursors, supported by appropriately designed bio-material scaffolds, could facilitate the development and enhancement of connections to ganglion cells and optic nerve axons. The consequence may be an improved retinal regeneration. This technique could also offer the possibility for retinal regeneration in treating other forms of optic nerve ailments through RGC replacement.

Methods: In this brief review, we describe the innovations and recent developments in retinal regenerative medicine such as retinal organoids and gene therapy which are specific to glaucoma treatment and focus on the selection of appropriate bio-engineering principles, biomaterials and cell therapies that are presently employed in this growing research area.

Results: Identification of optimal sources of cells, improving cell survival, functional integration upon transplantation, and developing techniques to deliver cells into the retinal space without provoking immune responses are the main challenges in retinal cell replacement therapies.

Conclusion: The restoration of visual function in glaucoma patients by the RGC replacement therapies requires appropriate protocols and biotechnology methods. Tissue-engineered scaffolds, the generation of retinal organoids, and gene therapy may help to overcome some of the challenges in the generation of clinically safe RGCs.

Keywords: Biomaterials; Cell therapy; Glaucoma; Retinal ganglion cells; Tissue engineering.

Fig. 1

The schematics of sensory (visual) input into the bran showing RGCs receiving visual information from photoreceptors via bi-polar and retina amacrine cells to collectively transmit image forming and non-image forming visual information via the visual pathway to the brain [51] (copyright licensed provided). ONL: Outer nuclear layer, OPL: Outer plexiform layer, INL: Inner nuclear layer, IPL: Inner plexiform layer, GCL: Ganglion cell layer

Fig. 2

The schematics of drainage pathways of aqueous humour production in healthy eye (Creative commons licence). Image info: “Cause of Glaucoma” by National Eye Institute is licensed under CC BY 2.0

Fig. 3

Allogeneic RGCs transplantation from the healthy retinas into patients offers a possibility of improvement of retinal function in glaucoma sufferers [46] (copyright licensed provided)

Fig. 4

RGCs obtained, through an appropriate protocol, from stem cells help regain lost vision and compensate for areas in the eye damaged by glaucoma

Fig. 5

The schematic diagram of an artificial scaffold, acting as a cell support/delivery vehicle designed to mimic the natural micro-environment, facilitating axonal repair and helping to restore lost axonal connections and replacing lost/damaged RGCs