Visual pigments regeneration

In addition to entering the RPE from the circulation, all-lrany-retinol passes into the RPE cells through their apical surfaces during bleaching of ihodopsin in the ROS. This phase of the visual cycle is better characterized than the reverse step, namely the reverse flow of retinoid that culminates in visual pigment regeneration. 

Since the key to understanding visual pigment regeneration lies in obtaining an insight into how 11-cis-retinoid is formed from all-troiu-retinoid, this section is devoted to this difficult as yet unsolved problem. Under what circumstances do retinoids isomerize ... 

In contrast, photoisomerization as a means for visual pigment regeneration appears to be the rule in invertebrates (Schwemer ra/., 1971 Haraera/., 1981). 

Rando RR (1992) Molecular mechanisms in visual pigment regeneration. Photochem Photobiol 56 1145-1156... 

Saari JC (2000) Biochemistry of visual pigment regeneration The Friedenwald lecture. Investigative Ophthalmology and Visual Science 41 337-348. 

The regeneration in vivo of visual pigments is a complex and yet not well understood part of the process of dark adaptation. In vitro regeneration using isolated retinas,... 

This is the intermediate metabolite between retinol and tRA and is used in the visual cycle where 11 -cis-retinal binds with the protein opsin to form rhodopsin, the visual pigment. It is undetectable in mammalian and chick embryos, but present at very high levels in amphibian (11,12) and zebrafish eggs (13). It is not active in inducing pattern duplication in the regenerating amphibian limb (8). 

Fig. 4.18 The rhodopsin cycle. The bleaching of rhodopsin yields all-trans retinene (now more currently indicated as retinal), which must be isomerized to neoretinene b before it can regenerate the visual pigment. Alternatively, having been reduced to all trans vitamin A, the latter in turn must be isomerized to neovitamin Ab before it takes part in rhodopsin synthesis. Rod vision thus depends on the continuous stereoisomerization of all-trans retinene or vitamin A, or on the continuous replacement of these substances by new supplies of vitamin Ab from external sources (adapted from [196, 197])...

In the dark-adapted eyes of most animals, the retinoid stores in the RPE represent between 1 and 6 mol Eq of the retinal visual pigment. It is not known whether the magnitude of these stores depends on the vitamin A status of the animal, although it is probable that they serve as a reserve that protects the visual system from retinoid depletion under conditions of dietary deficiency. Since these stores typically contain up to 75% 11-m-retinyl ester, the provision of 11-cis isomer for visual pigment synthesis may also be important under certain circumstances. However, the presence of this isomer in the RPE is not critical for regeneration, which can proceed efficiently in the absence of appreciable supplies of 11-cis-retinyl ester [see Bridges (1976b) for further discussion of this question]. 

Saari JC, Garwin GG, vanHooser JP, Palczewski K (1998) Reduction of al -trans retinal limits regeneration of visual pigment in mice. Vision Res 38 1325-1333... 

The retinal pigment epithelium cells (RPE) of the retina form an epithelial cell layer that takes up retinol from choroid capillaries and stores it as retinyl esters, to be used as substrate for the generation of 11-ds-retinal. In the layer of rod and cone photoreceptor cells adjacent to the RPE, 11-ds-retinal combines covalently with the protein opsin to generate the visual pigment rhodopsin in rods and, similarly, iodopsin in cones. Each rod outer segment is densely packed with some 10 molecules of rhodopsin per cell. The small quantity of vitamin A stored in the retina would be inadequate to maintain vision were it not for the visual cycle, a process in which 11-ds-retinal is regenerated after... 

Meta II seems to have multiple pathways of decay, either going on to a longer-wavelength intermediate Meta III or decaying directly to the free all-trans-retinal plus opsin. " The decay of Meta 11 in situ appears to be slow and may be the rate-limiting step in the normal regeneration of the visual pigment. 

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