The Retinoid Cycle and Retinal Diseases


The ‘retinoid cycle’ is a complex recycling system that replenishes the 11‐cis‐retinal chromophore of rod and cone visual pigments after its isomerization to all‐trans‐retinal by light. Recycling takes place in retinal rod and cone photoreceptor outer segments and the retinal pigment epithelium. Correct functioning of the retinoid cycle is of fundamental importance in vertebrate vision.

Keywords: vitamin A; rhodopsin; cone pigments; retinitis pigmentosa; macular degeneration

Figure 1.

Rhodopsin (R), the photoreceptor molecule present in rod photoreceptors, at the centre of two pathways: phototransduction and the retinoid cycle. In phototransduction, R triggers a series of reactions (T, transducin; PDE, cGMP phosphodiesterase; CNG, cGMP‐gated channel), which return to the inactive state during the recovery phase. In the retinoid cycle, the chromophore of rhodopsin (11‐cis‐retinal) is regenerated.

Figure 2.

Bleaching of rhodopsin, a G‐protein‐coupled receptor consisting of seven transmembrane domains and the 11‐cis‐retinal chromophore, produces all‐trans‐retinal. Rhodopsin is depicted as immersed in the ROS membrane phospholipid bilayer, where the blue circles represent polar phospholipid head groups. The chromophore retinal (shown on the right) is covalently attached to the opsin polypeptide and buried inside rhodopsin in a tightly fitting hydrophobic pocket.

Figure 3.

Schematic representation of the retinoid cycle. For simplicity, only the main pathway (blue arrows) and the major components are shown. Red arrows point to genes in which mutations have been associated with human retinal diseases. Two naturally occurring canine models with retinoid cycle gene defects are shown in blue boxes. RESTs, or retinosomes, retinyl ester storage particles. ROS, the cellular organelle where rhodopsin is located. RPE, retinal pigment epithelium, where most components of the retinoid cycle are located. IPM, interphotoreceptor matrix, separating RPE and ROS.



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Further Reading

Filipek S, Stenkamp RE, Teller DC and Palczewski K (2003) G protein‐coupled receptor rhodopsin: a prospectus. Annual Reviews in Physiology 65: 851–879.

Garriga P and Manyosa J (2002) The eye photoreceptor protein rhodopsin. Structural implications for retinal disease. FEBS Letters 528: 17–22.

Heckenlively JR (1988) Retinitis pigmentosa. Philadelphia, JB: Lippincott.

McBee JK, Palczewski K, Baehr W and Pepperberg DR (2001) Confronting complexity: the interlink of phototransduction and retinoid metabolism in the vertebrate retina. Progress in Retinal Eye Research 20: 469–529.

Okada T, Ernst OP, Palczewski K and Hofmann KP (2001) Activation of rhodopsin: new insights from structural and biochemical studies. Trends in Biochemical Sciences 26: 318–324.

Phelan JK and Bok D (2000) A brief review of retinitis pigmentosa and the identified retinitis pigmentosa genes. Molecular Vision 6: 116–124.

Sullivan LS and Daiger SP (1996) Inherited retinal degeneration: exceptional genetic and clinical heterogeneity. Molecular Medicine Today 2: 380–386.

Thompson DA and Gal A (2003) Vitamin A metabolism in the retinal pigment epithelium: genes, mutations, and diseases. Progress in Retinal Eye Research 22: 683–703.

Useful Websites

Webvision (University of Utah): (The organization of the retina and the visual system).

Authors’ websites (Baehr W) and (Palczewski K).

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How to Cite close
Palczewski, Krzysztof, and Baehr, Wolfgang(Sep 2005) The Retinoid Cycle and Retinal Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0004067]