Patterning and Development of Photoreceptors in the Human Retina

Abstract

Humans rely on visual cues to navigate the world around them. Vision begins with the detection of light by photoreceptor cells in the retina, a light-sensitive tissue located at the back of the eye. Photoreceptor types are defined by morphology, gene expression, light sensitivity, and function. Rod photoreceptors function in low-light vision and motion detection, and cone photoreceptors are responsible for high-acuity daytime and trichromatic color vision. In this review, we discuss the generation, development, and patterning of photoreceptors in the human retina. We describe our current understanding of how photoreceptors are patterned in concentric regions. We conclude with insights into mechanisms of photoreceptor differentiation drawn from studies of model organisms and human retinal organoids.

Keywords: cone; human; macula; photoreceptor; retina; retinoic acid; rod; thyroid hormone.

FIGURE 1

Anatomy of the human eye. Diagram of a human eye with the light path represented as a rainbow. Inset sections represent the retinal cell types present in the macula (top) and the fovea (bottom). Key describes retinal cell types.

FIGURE 2

Photoreceptor morphology. Schematic representation of rod photoreceptors (yellow), S (blue), M (green), and L (red) cone photoreceptors.

FIGURE 3

Opsin absorption and comparative morphology. (A) Relative absorption spectra of opsins with labeled peaks for S cones (blue, 420 nm), Rods (black, 498 nm), M cones (green, 534 nm), and L cones (red, 564 nm) adapted from (Bowmaker et al., 1980). (B) Pairwise comparisons of amino acids between the visual opsin proteins adapted from (Nathans et al., 1986b). Dark circles indicate amino acid differences. Sequences were optimally aligned such that no insertions or deletions were required except for comparing the carboxy termini between the green or red and blue pigments.

FIGURE 4

Retinal cell birth order. Adapted from (Lu et al., 2020). Cells per 10k = expected cells in 10k of cells. Day = Day post conception. Hgw = Human gestation week. Hpnd = Human postnatal day.

FIGURE 5

Retina morphology. Flat mount diagram of a human retina. Optic disc measurements were derived from (Arora et al., 2015), while macula, fovea, foveola, and outer rim measurements from (Schultze, 1866; Polyak, 1941; Curcio et al., 1990; Curcio et al., 1991; Hendrickson, 1992). Red lines indicate vasculature.

FIGURE 6

Patterning and migration of cones during development. (A) Heat map of cone density modeled from (Curcio et al., 1990). Cones range from 0 to 16,000 cells/mm² at intervals of 1,000 cells/mm². Densities above 16,000 cells/mm² are represented by gray. (B) Heat map of rod density modeled from (Curcio et al., 1990). Rods range from 0 to 200,000 cells/mm² at intervals of 12,500 cells/mm² (C) Graph of fetal age and onset of S and M/L cones by percent retinal coverage, adapted from (Xiao and Hendrickson, 2000). (D) S and M/L specification by onset of opsin protein during fetal retinal development modeled from (Xiao and Hendrickson, 2000). Gray area is growing retinal tissue representing retinal progenitors. Fwk = fetal week. F = fovea center, black oval = optic disc.