2026-02-18 ジョンズ・ホプキンス大学
<関連情報>
- https://hub.jhu.edu/2026/02/18/retina-organoids-human-vision/
- https://www.pnas.org/doi/10.1073/pnas.2510799123
ヒト中心窩錐体サブタイプのパターン形成における細胞運命の規定と遷移メカニズム A cell fate specification and transition mechanism for human foveolar cone subtype patterning
Katarzyna A. Hussey, Kiara C. Eldred, Brian Guy, +6 , and Robert J. Johnston Jr.
Proceedings of the National Academy of Sciences Published:February 13, 2026
DOU:https://doi.org/10.1073/pnas.2510799123
Significance
You are reading this text using your foveola, the central region of your eye that enables high-acuity vision. Though the foveola only makes up ~2% of the human retina, it is responsible for ~50% of our visual perception. The foveola is highly susceptible to impairment in diseases such as macular degeneration. The foveola is notable for its dense packing of green and red cone photoreceptors and exclusion of blue cones and rods. Here, we investigated the mechanisms that generate foveolar patterning of human cone photoreceptors. Our findings suggest that patterning of the green/red cone-rich foveola is generated by 1) limiting blue cone specification and 2) transitioning sparse blue cones to green/red cone fate.
Abstract
In the central region of the human retina, the high-acuity foveola is notable for its dense packing of green (M) and red (L) cones and absence of blue (S) cones. To identify mechanisms that pattern cones in the foveola, we examined human fetal retinas and differentiated retinal organoids. During development, sparse S-opsin-expressing cones are initially observed in the foveola. Later in fetal development, the foveola contains a mix of cones that either coexpress S- and M/L-opsins or exclusively express M/L-opsin. In adults, only M/L cones are present. Two signaling pathway regulators are highly and continuously expressed in the central retina: Cytochrome P450 26 subfamily A member 1 (CYP26A1), which degrades retinoic acid (RA) and Deiodinase 2 (DIO2), which promotes thyroid hormone (TH) signaling. Both CYP26A1 mutant organoids and high RA conditions increased the number of S cones and reduced the number of M/L cones in retinal organoids. In contrast, sustained TH signaling promoted the generation of M/L-opsin-expressing cones and induced M/L-opsin expression in S-opsin-expressing cones, showing that cone fate is plastic. Our data suggest that CYP26A1 degrades RA to specify M/L cones and limit S cones and that continuous DIO2 expression sustains high levels of TH to transition S-opsin-expressing cones into M/L cone fate, resulting in the foveola containing only M/L cones. Given the vulnerability of the foveola in macular degeneration and other retinal disorders, these findings provide a mechanistic framework for engineering organoids for therapeutic applications.
