The Rise of Retinal Organoids for Vision Research

Abstract

Retinal degenerative diseases lead to irreversible blindness. Decades of research into the cellular and molecular mechanisms of retinal diseases, using either animal models or human cell-derived 2D systems, facilitated the development of several therapeutic interventions. Recently, human stem cell-derived 3D retinal organoids have been developed. These self-organizing 3D organ systems have shown to recapitulate the in vivo human retinogenesis resulting in morphological and functionally similar retinal cell types in vitro. In less than a decade, retinal organoids have assisted in modeling several retinal diseases that were rather difficult to mimic in rodent models. Retinal organoids are also considered as a photoreceptor source for cell transplantation therapies to counteract blindness. Here, we highlight the development and field’s improvements of retinal organoids and discuss their application aspects as human disease models, pharmaceutical testbeds, and cell sources for transplantations.

Brain and Retinal Organoids for Disease Modeling: The Importance of In Vitro Blood–Brain and Retinal Barriers Studies

“…An obvious advantage of organoid cultures for disease modeling, compared with traditional cell cultures of a single cell type, is their ability to mimic large quantities of pathologies by recapitulating specific human features that could be relevant for translational studies [ 191 ]. Brain organoids represent a powerful in vitro approach to model brain development [ 35 , 108 , 192 ], understand neurodevelopmental diseases [ 193 ], recapitulate aspects of neurodegenerative diseases [ 194 , 195 , 196 , 197 ], and for personalized drug screening when an individual’s hiPSCs are used [ 49 , 198 ]; while retinal organoids have been reported as human eye disease models, pharmaceutical testbeds, and cell sources for transplantations [ 5 , 82 , 84 , 98 , 100 , 199 , 200 ].…”

“…In this review, we summarized the analytical methods applied in the brain as well as in retinal organoids research and, based on the disadvantages (e.g., reduced throughput and difficult sample preparation), we assess the necessity of improving certain techniques, which, in turn, allow accurate disease modeling. We review that these organoids are effective in vitro tools for disease modeling: while brain organoid technology has greatly enhanced neurodegenerative and neurodevelopmental disease and psychiatric disorders research [ 193 , 205 ], also the retinal organoid has improved visual research [ 5 , 200 ]. Indeed, we highlight that organoids from hPSCs-based retinal and brain organoids provide an outstanding opportunity to explore cellular and subcellular functions within in vitro models that closely recapitulate the native 3D configuration of the human neural tissue [ 22 ].…”

Neuartige Wirkstoffabgabesysteme für die Glaukomtherapie: Hürden und Lösungsansätze für die Formulierung

“…Aus Stammzellen gewonnene Photorezeptoren können weiterentwickelt werden, z.B. durch die Expression von optogenetischen Instrumenten zur Untersuchung der funktionalen Integration in die Empfänger-Netzhaut [380]. Während neu integrierte Photorezeptoren nur kurze Verbindungen zu den darunter liegenden Horizontal- und Bipolarzellen brauchen, müssen RGC lange Axone ausbilden und funktionelle Verbindungen zu spezifischen Zielen im Gehirn herstellen [381].…”

Novel Drug Delivery Systems Fighting Glaucoma: Formulation Obstacles and Solutions

“…Photoreceptors derived from retinal organoids have great potential for therapeutic photoreceptor transplantation. Stem cell-derived photoreceptors can be further developed, for example, by expressing optogenetic tools to study functional integration into the host retina [ 380 ]. While newly integrated photoreceptors require only short connections to the underlying horizontal and bipolar cells, RGCs need to elongate long axons and restore functional connections to their specific brain targets [ 381 ].…”