Retinoid cycle in the vertebrate retina: experimental approaches and mechanisms of isomerization

Abstract

Retinoid cycle describes a set of chemical transformations that occur in the photoreceptor and retinal pigment epithelial cells. The hydrophobic and labile nature of the retinoid substrates and the two-cell chromophore utilization-regeneration system imposes significant constraints on the experimental biochemical approaches employed to understand this process. A brief description of the recent developments in the investigation of the retinoid cycle is the current topic, which includes a review of novel results and techniques pertaining to the retinoid cycle. The chemistry of the all-trans-retinol to 11-cis-retinol isomerization is also discussed.

Metabolic Basis of Visual Cycle Inhibition by Retinoid and Nonretinoid Compounds in the Vertebrate Retina

“…This idea is also consistent with the proposed molecular mechanism for the isomerization reaction (reviewed in Ref. 49).…”

“…Protonation of retinoid followed by an elimination reaction leads to delocalization of the positive charge throughout the conjugated double bonds, thereby lowering the energy requirement for the conformational change needed for 11-cis-retinoid formation (3,72) (reviewed in Ref. 49). Ret-NH 3 ϩ might mimic the transition state proposed for this carbocation mechanism, and hence any modifications of the amino group would reduce the potency of this inhibitor.…”

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis

“…Mitochondrial β-oxidation, which is present in the RPE (74), is considered to be the major pathway that metabolizes fatty acids as a primary source of energy production (75,76). Since the RPE is involved in the light-induced retinoid cycle (77,78), one of the possible consequences of mitochondrial dysfunction in AMD may manifest as a disorder of light-induced retinoid recycle. Mitochondrial alterations were also accompanied by proliferation of peroxisomes.…”

Melanopsin Is Highly Resistant to Light and Chemical Bleaching in Vivo

“…All opsins utilize cis-to-trans isomerization of the retinaldehyde chromophore as the primary photoreceptive event and must regenerate the cis chromophore to regain photosensitivity. Although photocycles for chromophore regeneration of rhodopsin and, to a lesser extent, cone opsins are well understood (9), the mechanisms of melanopsin pigment regeneration are less well studied (10 -12). Previous work demonstrated that melanopsin can function independently of the retinal pigmented epitheliumbased photocycle that forms the basis for all rod and most cone pigment regeneration (1).…”