Spatial and temporal expression of cone opsins during monkey retinal development

Abstract

The primate retina requires a coordinated series of developmental events to form its specialized photoreceptor topography. In this study, the temporal expression of cone photoreceptor opsin was determined in Macaca monkey retina. Markers for mRNA and protein that recognize short wavelength (S) and long/medium wavelength (L/M) opsin were used to determine (1) the temporal and spatial patterns of opsin expression, (2) the spatial relationship between S and L/M cones at the time of initial opsin expression, and (3) the relative time of cone and rod opsin expression (Dorn et al. [1995] Invest. Ophthalmol. Vis. Sci. 36:2634-2651). Adult cone outer segments were recognized by either L/M or S opsin antiserum. Of all adult cone inner segments, 88-90% contained L/M opsin mRNA, whereas 10-12% contained S opsin mRNA. Fetal cones initially showed cell membrane as well as outer segment labeling for opsin protein, but cell membrane labeling disappeared by birth. No cones at any age contained markers for both S and L/M opsin mRNA or protein. S and L/M opsin protein appeared in the fovea at fetal day 75. Once opsin expression progressed beyond the fovea, both mRNA and protein for S opsin were consistently detected more peripherally than L/M opsin. Cones at the peripheral edge of S opsin expression had basal telodendria that appeared to reach toward neighboring cones. Because interactions between cone populations could organize the cone mosaic, the spatial relationship between S cones and the first cones to express L/M protein was analyzed quantitatively by using double-label immunocytochemistry. No consistent relationship was found between these two cone populations. Cones are generated at least 1 week before rods across monkey retina. However, rod opsin protein appears in and around the fovea at fetal day 66, 1 week before cone opsin protein. This suggests that independent local factors control differentiation in these two photoreceptor populations.

Topography of the long- to middle-wavelength sensitive cone ratio in the human retina assessed with a wide-field color multifocal electroretinogram

“…Nathans et al (1989) have proposed that the LCR binds to an L or M gene promoter by an entirely random process; however, the observed foveal-toperipheral gradient of increasing L:M ratio represents a non-random feature of opsin gene expression. This gradient parallels central to peripheral developmental processes (LaVail et al, 1991;Bumsted et al, 1997;Martin et al, 2000;Xiao & Hendrickson, 2000). Chromatin remodeling is associated with differentiation and controls activation and silencing of gene expression in an ongoing, dynamic process that occurs before and after cells undergo their final cell division (Ringrose & Paro, 2004).…”

“…Differences between S cones and L/M cones indicate that they are indeed different cell types (Bumsted et al, 1997;Bumsted & Hendrickson, 1999;Xiao & Hendrickson, 2000). However, L and M cones appear to represent a single cell type for which the final identity as an L versus M cone is simply determined by the opsin gene that is expressed (Nathans, 1999;Wang et al, 1999;Smallwood et al, 2002).…”

L and M Cone Contributions to the Midget and Parasol Ganglion Cell Receptive Fields of Macaque Monkey Retina

“…There is no evidence that midget bipolar cells, which are the middle elements in the private line connections from cones to midget ganglion cells, have selective surround circuitry. Additionally, during development, bipolar dendrites are stratified in the outer plexiform layer and synaptic markers are present well before L or M cone opsins are expressed, consistent with the formation of retinal circuitry before cone type is established (Okada et al, 1994;Bumsted et al, 1997). Finally, psychophysically measured red-green color sensitivity decreases more rapidly with increasing retinal eccentricity than would be expected from the loss of achromatic sensitivity (Mullen, 1991;Mullen andKingdom, 1996, 2002).…”

A moving wave patterns the cone photoreceptor mosaic array in the zebrafish retina

“…Although the human retina is rod-dominant in the periphery of the retina, the macula, which is most critical for functional vision, is strongly conedominant. Thus, the failure of cone photoreceptors to develop properly or the subsequent loss of cone function in humans has the most severe consequences on visual abilities (Neitz and Neitz, 2000;Aiello, 2003;Ambati et al, 2003;Pacione et al, 2003).Cone photoreceptor development has been studied in a few animal models that have abundant cones in addition to rod photoreceptors, most notably primates (Bumsted et al, 1997;Sears et al, 2000), chicks (Bruhn and Cepko, 1996;Adler et al, 2001), and teleost fishes (Branchek and BreMiller, 1984;Larison and BreMiller, 1990;Raymond et al, 1995;Schmitt and Dowling, 1996). Unlike rod photoreceptors, which except in some amphibians all express the same visual pigment gene (rod opsin or rhodopsin), different subtypes of cone photoreceptors express different cone opsin genes that generate visual pigments with varying spectral absorption maxima (Yokoyama, 2000;Cook and Desplan, 2001;Ebrey and Koutalos, 2001).…”

“…1) that only develop with further maturation of the cone photoreceptors. However, the expression of opsin and other proteins of the transduction cascade are a relatively late event in the differentiation of photoreceptors in fish (Stenkamp et al, 1996) as in other vertebrates (Hauswirth et al, 1992;Bumsted et al, 1997;Sears et al, 2000), so it is possible that commitment to a specific spectral cell subtype occurs at an even earlier stage. The molecular mechanisms that control cell-fate choice among cone spectral subtypes in the zebrafish retina and the source of the patterning information are unknown.…”