Retinal organoids as models for development and diseases

Abstract

The evolution of pluripotent stem cell-derived retinal organoids (ROs) has brought remarkable opportunities for developmental studies while also presenting new therapeutic avenues for retinal diseases. With a clear understanding of how well these models mimic native retinas, such preclinical models may be crucial tools that are widely used for the more efficient translation of studies into novel treatment strategies for retinal diseases. Genetic modifications or patient-derived ROs can allow these models to simulate the physical microenvironments of the actual disease process. However, we are currently at the beginning of the three-dimensional (3D) RO era, and a general quantitative technology for analyzing ROs derived from numerous differentiation protocols is still missing. Continued efforts to improve the efficiency and stability of differentiation, as well as understanding the disparity between the artificial retina and the native retina and advancing the current treatment strategies, will be essential in ensuring that these scientific advances can benefit patients with retinal disease. Herein, we briefly discuss RO differentiation protocols, the current applications of RO as a disease model and the treatments for retinal diseases by using RO modeling, to have a clear view of the role of current ROs in retinal development and diseases.

Retinal Organoids and Retinal Prostheses: An Overview

“…As previously reviewed by Zhang et al, 24 studies have so far modelled several aspects of retinal diseases using 3D ROs either derived from patients or from genetically manipulated PSCs. These diseases include retinitis pigmentosa, Leber’s congenital amaurosis, glaucoma, macular telangiectasia type 2, microphtalmia, retinoblastoma, Stargardt disease, and X-linked juvenile retinoschisis [ 163 ].…”

“…Surprisingly, we were unable to find any publication that directly intersected both fields. As mentioned earlier in this review, ROs can now represent key features of the native human retina and are currently used as disease models to decipher specific disease mechanisms to treat or reverse retinal degeneration [ 12 , 163 ]. In addition, few studies employed electrode arrays to show that hiPSCs-derived ROs are light-responsive [ 92 , 100 ], proving the applicability of ROs as in vitro models.…”

Harnessing the Neuroprotective Behaviors of Müller Glia for Retinal Repair

“…In vitro technologies, including cell cultures [65][66][67], microfluidic devices [68,69], organoids [70][71][72], and others [73,74], can be applied to study the morphology, migration, proliferation, and/or cell interconnectivity of retinal cells with high precision (Reviewed in [75]). Physiological changes in retinal cells can also be studied as a function of time within these same models, which is not possible in vivo.…”

Functional microglia derived from human pluripotent stem cells empower retinal organs

“…The DCL mainly includes amacrine and horizontal cells and newborn RGCs along the basal surface, whereas the NbL contains primarily retinal progenitor cells, which would differentiate into bipolar, Müller and photoreceptor cells along the apical surface in late stages (Abud et al, 2017;Nakano et al, 2012). Retinal organoids provide an excellent research tool to address fundamental questions, understand disease delineation and discover new drugs (Capowski et al, 2019;Cora et al, 2019;Deng et al, 2018;DiStefano et al, 2018;Hallam et al, 2018;Jin et al, 2019;Kim et al, 2019;Reichman et al, 2017;Völkner et al, 2016;Wang et al, 2021;Zhang et al, 2021b). However, microglia, the key neuro-immune cells regulating the natural microenvironment of the retina, are completely absent from the currently developed retinal organoids (Collin et al, 2019;Sridhar et al, 2020), which made the organoids less representative of real retinas.…”