Interstitial retinol-binding protein

Transport of all-trans-retinol to the Apical Surfaces of the RPE Cells—Interstitial Retinol-Binding Protein, a Glycoprotein Synthesized by the Retina... 

Although it has been shown to be capable of binding retinaldehyde and retinoic acid (Liou et al., 1982c), as well as a-tocopherol (Liou et al., 1983), the major endogenous ligand of interstitial retinol-binding protein appears to be... 

Fig. 12. Absorption spectrum of interstitial retinol-binding protein. E330 = 1.14 x 1(P M cm corresponding to between 2 and 3 mol of all-rrons-retinol per mol of protein. (From Fong etal.. 1983b.)...

Interstitial retinol-binding protein may correspond to a 7-8 S receptor for exogenous [ HJretinol assigned to bovine retina cytosol and brain by Wiggert et al. (1978), to bovine ROS by Lee and Wiggert (1982), and to the interphotoreceptor matrix by Lai et al. (1982). For further discussion, see Liou et al. (1982c). 

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. 

Interstitial retinol-binding protein may also carry other lipid-soluble ligands vitamin E is one possibility (Seetion II,F,2). This compound is present in bovine... 

The cause or causes of retinitis pigmentosa are yet to be found and at present a possible role for vitamin A in this condition has not been established. However, the above studies have enabled us to eliminate some possibilities and to identify others. The retinitis pigmentosa eye was normal in its ability to store retinoid, to esterify retinol, and to convert the all-trans isomer to 11-cis. A major abnormality was the absence of interstitial retinol-binding protein. It has not been established whether this is a selective loss, or whether other components of the interphotoreceptor matrix are also involved. Clearly, much more woric is needed before we arrive at an insight into the causes of chorioretinal binding diseases. 

All-trans retinol then diffuses out of the outer segments (rod or cone) and into the retinal pigmented epithelium (RPE). The diffusion of all-trans-retinol out of the outer segments and into RPE cells is facilitated by interstitial retinoid binding protein (IRBP), which is localized in the extracellular matrix of the retina (22). IRBP binds all-trans-retinol as it diffuses out of the outer segment cells and is believed to facilitate transport of aM-trans-retinol to the RPE cell. Additionally, RPE cells directly acquire retinol from serum as described earlier. In both cases, retinol in the RPE cell is rapidly esterified by LRAT in a lecithin-dependent mechanism (22). Retinyl esters provide both a mechanism of storage for the RPE cell and/or provide a substrate for the isomerization reaction (22). 

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