Saturday, February 12, 2022

Retinal Organoid Cones with Robust Phototransduction

Article: UW study finds photoreceptor cells from retinal organoids can replicate key functions of vision
Source: University of Wisconsin-Madison, Medicine
Published: February 2, 2022

Retinal organoid and its photoreceptors tagged for gene expression of various proteins

Retinal organoids, miniature versions of eye structures grown in vitro from stem cells, have been explored as a model for studying eye development as well as testing and treating various eye diseases. However, growing the correct cell types and in the correct arrangement does not necessarily show that the artificially grown cells are able to replicate fundamental functions of native tissue, such as detecting light. In a recent study, scientists demonstrated for the first time that cone photoreceptors in retinal organoids grown from human pluripotent stem cells (hPSCs) had robust, graded, wavelength-specific electrophysiological responses to light "akin to adult foveal cones." That is, these cells could initiate phototransduction, the first step to vision. Furthermore, the lab-generated cones showed membrane physiology comparable with those of intact ex vivo primate foveas. The authors also note that the retinal organoid cones, which were allowed to mature in the lab for eight months for uniformity, were most sensitive to light detection at the latest stages of maturation. One of the researchers comments, "We went from important early studies showing weak light responses in rod photoreceptors that mediate dim light vision to seeing the potential for responses to light in the cone cells that humans rely on the most. The cells responded robustly, and could differentiate between red, green and blue light, just like in normal human cones. It’s really quite remarkable." They next plan to improve the sensitivity of the retinal organoid cones as well as develop organoid models to study retinal degenerative diseases such as retinitis pigmentosa and macular degeneration.

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Saha A, Capowski E, Fernandez Zepeda MA, et al. "Cone photoreceptors in human stem cell-derived retinal organoids demonstrate intrinsic light responses that mimic those of primate fovea." Cell Stem Cell.  30 January 2022. https://doi.org/10.1016/j.stem.2022.01.002

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