Abstract
SummaryLoss of cone photoreceptors, crucial for daylight vision, has the greatest impact on sight in retinal degeneration. Transplantation of stem cell-derived L/M-opsin cones, which form 90% of the human cone population, could provide a feasible therapy to restore vision. However, transcriptomic similarities between fetal and stem cell-derived cones remain to be defined, in addition to development of cone cell purification strategies. Here, we report an analysis of the human L/M-opsin cone photoreceptor transcriptome using an AAV2/9.pR2.1:GFP reporter. This led to the identification of a cone-enriched gene signature, which we used to demonstrate similar gene expression between fetal and stem cell-derived cones. We then defined a cluster of differentiation marker combination that, when used for cell sorting, significantly enriches for cone photoreceptors from the fetal retina and stem cell-derived retinal organoids, respectively. These data may facilitate more efficient isolation of human stem cell-derived cones for use in clinical transplantation studies.
Highlights
Retinopathies featuring the progressive degeneration of the rod and cone photoreceptor cells lead to permanent blindness
cone-rod homeobox gene (CRX) and RECOVERIN protein were detected in the 9–19 pcw retina, with a greater density of highly expressing cells in the central retinal region compared with the periphery (Figure S1B)
GNAT2 localized to the apical region of the outer nuclear layer (ONL) in cone developing outer segments (Figure 1I); RXRG localized to the outermost cone cell bodies of the central ONL (Figure 1J), whereas rod markers, NRL and NR2E3, showed distinct immunostaining of developing rod cell bodies (Figures 1K and S1D)
Summary
Retinopathies featuring the progressive degeneration of the rod and cone photoreceptor cells lead to permanent blindness. Inherited retinal dystrophies affect 1 in 3,000 people worldwide (Bessant et al, 2001), with the most common form, retinitis pigmentosa, presenting with primary rod degeneration followed by the loss of cones. Agerelated macular degeneration results in the primary loss of cones in the macula. Cone degeneration has the greatest impact on sight since cones are fundamental for the detection of color, daylight vision, and high visual acuity. The human retina contains three different types of cone photoreceptors; approximately 5%–10% of the cone population express S-opsin, while the majority of cones (90%–95%) express either L-opsin or M-opsin light-sensitive proteins (Craft et al, 2014). Even though cone photoreceptors are a rare population, forming 2%–4% of total retinal cells, humans are dependent on these cells for optimal vision
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
