ABSTRACT

In vertebrates, both rod and cone visual pigments require 11-cis-retinal as a chromophore [1]. Upon absorption of photon, 11-cis-retinal photoisomerizes to all-transretinal, which triggers the conformational change of opsin, activating G-protein transducin and initiating vision [1,2]. The recycling of 11-cis-retinal termed the visual cycle is a key process in the regeneration of visual pigments (for reviews, see [3-5]; Figure 2.1). All-trans-retinal generated by photoactivation is dissociated from opsin and converted to all-trans-retinol by all-trans-retinol dehydrogenase [6,7]. The alltrans-retinol is then exported from photoreceptors to the retinal pigment epithelium (RPE) through the interphotoreceptor matrix [3,5]. In the RPE cells, all-trans-retinol is esteri˜ed to all-trans-retinyl esters [8]. The key enzyme of the visual cycleisomerohydrolase-processes all-trans-retinyl esters into 11-cis-retinol [9,10]. The chemical nature of the isomerohydrolase was unknown for a long time. Recently, we and two other groups reported that the protein RPE65 possesses isomerohydrolase activity [11-13] (see the following text). Our recent study shows that puri˜ed RPE65 constituted into liposomes displays robust isomerohydrolase activity and thus provides conclusive evidence that RPE65 is the isomerohydrolase in the visual cycle [14]. There are two possible pathways for 11-cis-retinol in the RPE: the ˜rst pathway is to be esteri˜ed and stored as retinyl ester in the RPE [3,5] and the second is for

2.1 Introduction ....................................................................................................23 2.2 Transportation of All-trans-Retinal out of Rod Outer Segments ...................24 2.3 All-trans-Retinal Reduction in Photoreceptors ..............................................25 2.4 Retinoid Transfer between Photoreceptors and RPE ......................................27 2.5 Esteri˜cation of All-trans-Retinol in the RPE by Lecithin:

Retinol Acyltransferase ...................................................................................27 2.6 Generation of 11-cis-Retinol in the RPE ........................................................29 2.7 Oxidation of 11-cis-Retinol in the RPE .......................................................... 33 2.8 Summary and Conclusion ............................................................................... 35 References ................................................................................................................36