Cone Photoreceptors in Human Stem Cell-derived Retinal Organoids Demonstrate Intrinsic Light Responses That Mimic Those of Primate Fovea

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2022 Feb 1

PMID 35104442

Authors

Aindrila Saha

Elizabeth Capowski

Maria A Fernandez Zepeda

Emma C Nelson

David M Gamm

Raunak Sinha

Affiliations

Soon will be listed here.

Abstract

High-definition vision in humans and nonhuman primates is initiated by cone photoreceptors located within a specialized region of the retina called the fovea. Foveal cone death is the ultimate cause of central blindness in numerous retinal dystrophies, including macular degenerative diseases. 3D retinal organoids (ROs) derived from human pluripotent stem cells (hPSCs) hold tremendous promise to model and treat such diseases. To achieve this goal, RO cones should elicit robust and intrinsic light-evoked electrical responses (i.e., phototransduction) akin to adult foveal cones, which has not yet been demonstrated. Here, we show strong, graded, repetitive, and wavelength-specific light-evoked responses from RO cones. The photoresponses and membrane physiology of a significant fraction of these lab-generated cones are comparable with those of intact ex vivo primate fovea. These results greatly increase confidence in ROs as potential sources of functional human cones for cell replacement therapies, drug testing, and in vitro models of retinal dystrophies.

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