Cone Photoreceptor Transplantation in Mice

Article: Cones Derived from Human Stem Cells Help Mice See
Source: The Scientist, King's College London
Published: April 23, 2021

Wild-type cones generate widespread mERG
and light-evoked spiking activity

Researchers in the U.K. conducted a proof-of-concept study that restored some degree of vision in mouse eyes transplanted with cone photoreceptors derived from human embryonic stem cells. Previous studies have transplanted stem cells that replaced the retina's pigmented epithelium, or converted mouse skin cells directly into rod photoreceptors. The present work is the first study to transplant retinal cells using using cone photoreceptors, which the authors emphasized for their importance in central and color vision. The researchers developed to variants of human cones: a normal type derived from human embryonic stem cells and a control derived from the peripheral blood of a 40-year-old person with achromatopsia. The functional cone photoreceptors were injected into the retinas of 32 mouse eyes, and the aberrant cones were injected into the retinas of 23 mouse eyes. As an additional study design quality measure, the mice were bred to have advanced eye disease with complete nonfunctional cones to control for the possibility of residual function from existing cones, rather than the transplanted cones. Both types of cones attached to the mice's retinas. Testing with microelectroretinogram, however, showed that only the functional human cones responded to light. Furthermore, only the mice that received functional cones exhibited behavioral responses to light, such as retreating to a dark room in the presence of light, a natural response for these nocturnal animals. The researchers next plan to improve the manufacturing capacity of cone photoreceptors, and they hope to start clinical trials several years in the future.

Personal commentary: While there is no evidence or grounds to support a desire for clinical trials, the investigators' effort demonstrates the strength of their motivation to prevent disease.

My rating of this study: ⭐⭐⭐

Ribeiro J, Procyk CA, West  EL, et al. "Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors." Cell Reports.  35(3):109022. 20 April 2021. https://doi.org/10.1016/j.celrep.2021.109022