Retina retinaldehyde

In the retina, retinaldehyde functions as the prosthetic group of the light-sensitive opsin proteins, forming rhodopsin (in rods) and iodopsin (in cones). Any one cone cell contains only one type of opsin and is sensitive to only one colour of light. Colour blindness results from loss or mutation of one or other of the cone opsins. 

Spom, Roberts and Goodman81 have recently provided a broad overview of the field of the retinoids, based on the IUPAC-IUB Joint commission definition that Retinoids are a class of compounds consisting of four isoprenoid units joined in a head-to-tail manner. (The work was updated in 1994) Whereas there is only a handful of naturally occurring retinoids using this definition, more than a thousand man-made retinoids are known. The IUPAC-IUB bulletin recommended that the term, retinal, not be used as a chemical designation but be reserved as an adjective referring to the retina. They suggested that retinaldehyde be used instead in scientific literature as the name of chemical related to vision. 

The main physiologically active forms of vitamin A are retinaldehyde and retinoic acid, both of which are derived from retinol. Retinaldehyde functions in the visual system as the prosthetic group of the opsins, which act as the signal transducers between reception of light in the retina and initiation of the nervous impulse. 

The pigment epithelium of the retina receives all- fraws-retinol fromplasma RBP. It is then isomerized to ll-c(s-retinol, which may either be stored as ll-c(s-retinyl esters or oxidized to ll-c(s-retinaldehyde, which is transported to the photoreceptor cells bound to an interphotoreceptor retinoid binding protein. 

After the light-catalyzed reaction, all-mins-rctinal is released, which in turn is reduced to all-/ntm-retinol. To be used again by opsin, the all-/nins-retinol must be converted to I l-eis-rclinol. Isomerization occurs in the pigment epithelium of the retina. Oxidation of I l-cis-relinol to I -cis-relrnaldchyde occurs while retinol is bound to the protein cellular retinaldehyde-binding protein (CRALBP) by a microsomal enzyme in the pigment epithelium. ... 

Bleaching of rhodopsin in bovine retina. Absorption of light by 11-cii-retinaldehyde initiates the configurational change to a -trans retinaldehyde, culminating in hydrolysis of the bond between retinaldehyde and Lys 53 of opsin. The order of formation of the intermediates is tentative. The symbol hv represents a photon of visible light. [Modified and reproduced, with permission, from C. D. B. Bridges, Retinoids in photosensitive systems. In The Retinoids, Vol. 2,... 

In the retinal cells of the eye, vitamin A (all-trans-retinol) is converted into the 11-ds-isomer, which is then oxidised to 11-cts-retinaldehde. In the dark the latter then combines with the protein opsin to form rhodopsin (visual purple), which is the photoreceptor for vision at low light intensities. When light falls on the retina, the czs-retinaldehyde molecule is converted back into the aW-trans form and is released from the opsin. This conversion results in the transmission of an impulse up the optic nerve. The all-frans-retinaldehyde is converted to all-trans-retinol, which re-enters the cycle, thus continually renewing the light sensitivity of the retina (Rg. 5.2). 

Among humans, abnormal dark adaptation is reported in both vitamin A deficiency and zinc deficiency and is especially prevalent in alcoholic cirrhotics (Patek and Haig, 1939 Russell et aL, 1973 Morrison et aL, 1978 McClain et aL, 1979). In the former but not in the latter deficiency, treatment with vitamin A reverses the abnormality (Russell et aL, 1978) only after correcting the zinc deficiency does dark adaptation become normal in the latter case (Morrison et aL, 1978 McClain et aL, 1979). The molecular basis for these observations may be associated, at least in part, with the activity of retinaldehyde reductase in the retina which, as already mentioned, Huber and Gershoff (1975) showed to be especially sensitive to the level of zinc nutriture and Mezey and Holt (1971) showed was competitively inhibited by the presence of ethanol. In the alcoholic cirrhotic, however, the zinc-vitamin A interaction may be further complicated by a defective hepatic synthesis of transport proteins (Mobarhan et aL, 1981) or failure to sequester or retain zinc Nutrition Reviews, 1982) and/or vitamin A (Sato and Lieber, 1981 Leo and Lieber, 1982) in the appropriate tissues. The implications for human nutrition of the interaction of vitamin A and zinc were reviewed by Solomons and Russell (1980). 

Saari, J. C. and Bredburg, D. L. (1987) Photochemistry and stereoselectivity of cellular retinaldehyde-binding protein from bovine retina. J. Biol. Chem. 262, 7618-7622. 

De Leeuw, M, Gaur, V. P., Saan, J. C., and Milam, A. H. (1990) Immunolocahzation of cellular retinol-, retinaldehyde- and retinoic acid-binding proteins in rat retina dunng pre- and postnatal development. 7 Afewrocyto/. 19,253-364. 

Crabb, J. W., Goldflam, S., Hams, S. E., and Saan, J. C. (1988) Cloning of the cDNAs encoding the cellular retinaldehyde-binding protein from bovine and human retina and comparison of the protein structures J. Biol Chem. 263,18,688-18,692. 

Saan, J C. and Bredberg, L D. (1988) Purification of cellular retinaldehyde-binding protein from bovine retina and retinal pigment epithelium. Exp Eye Res 46,569-578... 

Retinoic acid (Dl) is formed irreversibly from retinaldehyde (Futterman, 1962) and therefore is not a precursor for rhodopsin. Retinoic acid supports growth, promotes epithelial cell differentiation, and suppresses neoplastic development (e.g., Zile et al., 1979 Roberts and Frolik, 1979 Lotan, 1980). It occurs in the retina (Saari et al., 1982), but it is not known whether it has a speciflc retinal function. 

RPE (Saari et ai, 1977). This observation may imply that the RPE has no role in delivering retinoic acid to the retina. Retinoic acid is often generated within the tissue where it presumably carries out its function (Roberts and DeLuca, 1967 Olson, 1967). The retinoic acid that may be needed by the retina, where CRABP is abundant (Saari et al., 1977, 1982), may therefore be provided by oxidation of retinaldehyde. 

When rhodopsin is exposed to light it forms a series of intermediates, most of them transients at physiological temperatures (Section II,A, 1). The last intermediate, possibly V-retinylideneopsin, is unstable at physiological pH and hydrolyzes to opsin and all-rroitj-retinaldehyde. In the human retina at 36°C, free retinaldehyde has a half-life of 23 s (Baumann and Bender, 1973). This is because it is reduced to all-rrony-retinol by a membrane-bound dehydrogenase that may also act on the retinylideneimine compound (DePont et al., 1970). 

All-tra/w-retinol, 11-cw-retinol (A2) and 11-m-retinaldehyde are found in the 1PM (Liou et al., 1982c). At present, it is not clear which retinoid, or which isomer, is in transit from the RPE to the ROS. With regard to carrier proteins, the evidence suggests that CRBP and CRAIBP are present in the 1PM (Liou et al., 1982c), but it is probable that they have leached from the RPE and retina cytosols where both proteins occur. On the other hand, interstitial retinol-binding protein is believed to be a true IPM protein because it is absent from the RPE and retina cytosols. This conclusion has been confirmed by immunocytochemical observations in the author s laboratory (Fong et al., 1984) and by Bunt-Milam and Saari (1983). Although IRBP binds the all-tranj-retinol that is released when rhodop-sin is bleached, it also carries some 11-cis isomer, and it has not been established whether it may be implicated in the two-way transport of retinoids. 

All-trarti-retinoids are not able to support regeneration in frogs and mammalian retinas. The 11-cis retinoids that have been tested are retinaldehyde, retinol, and retinyl palmitate. 

Of particular interest is the fact that 11-c/s-ietinoid in bovine retina cytosol consists of 11-cis-retinol as well as 11-cw retinaldehyde. In contrast, only 11-c/s-retinaldehyde is present in the RPE cytosol [Saari (1982) Saari et al. (1982) see also Liou et al. (1982c)]. Since bovine and other mammalian retinas cannot utilize 1 l-cu-retinol for rhodopsin regeneration (see Section III,G,3), its... 

In the pigment epithelium of the retina, all-/ra j-retinol is isomerized to 11-cm-retinol and oxidized to 1 l-at-retinaldehyde. This reacts with a lysine residue in opsin, forming the holoprotein rhodopsin. Opsins are cell type specific they shift the absorption of 11-a r-retinaldehyde from the ultraviolet (UV) into what we call, in consequence, the visible range — either a relatively broad spectrum of sensitivity for vision in dim light (in the rods) or more defined spectral peaks for differentiation of colours in bright light (in the cones). 

---