Retinal Organoids and Retinal Prostheses: An Overview

Abstract

Despite the progress of modern medicine in the last decades, millions of people diagnosed with retinal dystrophies (RDs), such as retinitis pigmentosa, or age-related diseases, such as age-related macular degeneration, are suffering from severe visual impairment or even legal blindness. On the one hand, the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and the progress of three-dimensional (3D) retinal organoids (ROs) technology provide a great opportunity to study, understand, and even treat retinal diseases. On the other hand, research advances in the field of electronic retinal prosthesis using inorganic photovoltaic polymers and the emergence of organic semiconductors represent an encouraging therapeutical strategy to restore vision to patients at the late onset of the disease. This review will provide an overview of the latest advancement in both fields. We first describe the retina and the photoreceptors, briefly mention the most used RD animal models, then focus on the latest RO differentiation protocols, carry out an overview of the current technology on inorganic and organic retinal prostheses to restore vision, and finally summarize the potential utility and applications of ROs.

Keywords: 3D models; blindness; iPSCs; organic semiconductors; photovoltaic polymers; restore vision; retinal dystrophy; retinal organoids; retinal prosthesis.

Figure 1

(A) Cellular organization of the retina. The retina contains the retinal neuronal cell types, such as the retinal pigment epithelium (RPE), which faces choroidal blood vessels at the basal side, and cones (purple) and rods (blue) at the apical side. The photoreceptor nuclei constitute a layer called the outer nuclear layer (ONL), whereas their axons and processes meet with horizontal (violet) and bipolar (red) cells in the outer plexiform layer (OPL). More anterior, the inner nuclear layer (INL) harbors nuclei of the bipolar (red), amacrine (pink), and horizontal (violet) cells, and Müller glia, while the inner plexiform layer (IPL) contains the processes and synapses of bipolar (red) cells, amacrine (pink) cells, and retinal ganglion cells or RGCs that are reduced in number by the stage of photoreceptor maturation (yellow). (B) Structure of rod and cone photoreceptors. Photoreceptors are polarized sensory neurons. Rods (blue) and cones (red) have three cellular compartments. Outer segments (OS) are stacks of membrane disks rich in the visual pigment rhodopsin. This is where phototransduction originates. Interestingly, this cellular part does not contain any protein synthesis machinery. All OS proteins are synthesized in the inner segments (IS) and then transported to this cellular part. IS also contain other vital organelles, i.e., mitochondria, and the nucleus. Neuronal impulses created in the OS pass through the IS until they reach the synaptic terminals, where they are transmitted to other retinal neurons. (Created with BioRender.com).

Figure 2

Applications of retinal organoids in various research fields. Retinal organoids carry great potential to be utilized in many research areas, from genetic engineering, omics analyses, and drug development to developmental studies and cell therapy. Retinal organoids can also be used as human in vitro models and in the recent emergence of retina-on-a-chip technology. One additional potential utility is to test the efficiency of retinal prostheses, when retinal organoids are used as human in vitro models recapitulating the disease pathophysiology. Despite few studies proving that retinal organoids are light-responsive on electrode arrays, this application on retinal prostheses has not yet been addressed in any publication, which justifies the question mark in the figure. (Created with Biorender.com).