Retinoic Acid Synthesis in the Developing Chick Retina

Abstract

The transcriptional activator retinoic acid (RA) has been shown to influence the early patterning of the vertebrate eye. Models for the establishment of the retinofugal projection postulate gradients of cell-surface markers across the retinal surface that are expressed by ganglion cells and mediate the correct connection of fibers within central target fields. Spatial asymmetries of RA and RA-producing enzymes, as have been found in the eyes of mice and zebrafish, could induce the required asymmetry in gene expression. Here we exploited the large size of the retina of the embryonic chick to analyze the spatial and temporal characteristics of the RA system by HPLC in combination with a reporter cell assay. As in other embryonic vertebrates, the chick retina was found to contain different RA-generating enzymes segregated along the dorsoventral axis. The major RA isomer in both dorsal and ventral retina was all-transRA, and no 9-cisRA could be detected. This excludes a difference in production of these two isomers as an explanation for the expression of different RA-generating enzymes. At developmental stages embryonic days (E) 4 and 5, the ventral retina contained higher all-transRA levels than the dorsal retina. After E8, however, the difference disappeared, and in embryos at E9 and older the RA concentration was slightly higher in dorsal than ventral retina.

Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development

“…5B). These findings fit well with the established roles for RA in the development of the retina (14,16,25) and in RPE abnormalities found in Apc and Rxr␣ knockout mice (19,20). Loss of RA production in the developing retina offers an explanation for the presence of retinal defects, such as congenital hypertrophy͞hyperplasia of the retinal pigmented epithelium, commonly present in familial adenomatous polyposis patients.…”

“…The presence of severe ventral retinal defects and the absence of cellular differentiation in apc mutant embryos were highly reminiscent of retinoid deficiency (14,15,17,18,25). This finding, coupled with our previous findings that apc regulates RA production in the intestine, led us to hypothesize that retinoid deficiency underlies the defects present in apc mutant retinas.…”

Role of Purpurin as a Retinol-Binding Protein in Goldfish Retina during the Early Stage of Optic Nerve Regeneration: Its Priming Action on Neurite Outgrowth

“…These results strongly indicate that retinoic acid participates in retinol-bound purpurininduced neurite outgrowths. The importance of retinoic acid and RALDH-2 is well known in developing retina (Mey et al, 1997;Stull and Wikler, 2000) and adult mouse dorsal root ganglia (Corcoran and Maden, 1999). Recently, the activation of retinoic acid signaling after sciatic nerve injury was reported in rats (Zhelyaznik et al, 2003).…”

Direct gating by retinoic acid of retinal electrical synapses

“…Several lines of evidence have shown that RA is a potential endogenous neuroactive substance in the vertebrate retina including the presence of precursors, synthetic enzymes, binding proteins, nuclear receptors, and demonstrated RA release (3,4,6,(33)(34)(35)(36)(37)(38)(39). Because RA is membrane permeant, it is highly diffusible in tissue.…”