The retina, an integral part of the central nervous system (CNS), consists of seven different cell types, histologically organized in an evolutionarily conserved laminar structure, which are responsible for generating and transmitting the visual signal. For example, rod and cone photoreceptors (rods and cones, respectively) capture light reflected from an object and generate an electrical signal. This is subsequently relayed to retinal ganglion cells (RGCs) for transmission to higher centers in the brain for visual perception after having been modulated by the intervening neurons, the horizontal cells (HCs), bipolar cells (BCs), and amacrine cells (ACs). Müller glia (MG), the single glia generated by the multipotential retinal progenitor cells (RPCs), regulates the homeostasis of this highly metabolically active and energy-demanding tissue. The non-neuronal retinal pigment epithelium (RPE), located outside the retina, yet in intimate contact with photoreceptors, plays a critical role in the structural and functional viability of these cells.
Fig.1 Schematic overview of in vivo and ex vivo approaches to regenerative medicine through recapitulating developmental mechanisms. (Ahmad, 2020)
The loss of the visual signal when photoreceptors degenerate in age-related macular degeneration (AMD) or retinitis pigmentosa (RP) or the lost ability to transmit it to the brain when RGCs degenerate in glaucoma invariably leads to blindness. Unfortunately, there is no effective treatment to reverse the loss of vision when photoreceptors or RGCs die. However, transformative research over the last twenty years has led to discoveries that are promising for regenerative medicine for retinal degeneration: self-organization of pluripotent stem cells into 3D retinal organoids, providing platforms for disease modeling and cells for retinal repair. When combined with drug screening, disease modeling using iPSC lines from patients of different genetic backgrounds with retinal degeneration of familial and sporadic origins has the potential for (1) clinical trial in a dish, the depth and breadth of which is not fully achievable in regular clinical trials, and (2) prospectively selecting patients for personalized treatment. These findings suggest that strategies could be formulated for practical and personalized regenerative medicine with the purpose of recovering and preventing vision loss due to degenerative changes in diverse populations of patients.
Fig. 2. Summary of potential applications of retinal organoids. (Llonch, 2018)
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