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Vitamin A and Vision

Part of the Subcellular Biochemistry book series (SCBI,volume 81)

Abstract

Visual systems detect light by monitoring the effect of photoisomerization of a chromophore on the release of a neurotransmitter from sensory neurons, known as rod and cone photoreceptor cells in vertebrate retina. In all known visual systems, the chromophore is 11-cis-retinal complexed with a protein, called opsin, and photoisomerization produces all-trans-retinal. In mammals, regeneration of 11-cis-retinal following photoisomerization occurs by a thermally driven isomerization reaction. Additional reactions are required during regeneration to protect cells from the toxicity of aldehyde forms of vitamin A that are essential to the visual process. Photochemical and phototransduction reactions in rods and cones are identical; however, reactions of the rod and cone visual pigment regeneration cycles differ, and perplexingly, rod and cone regeneration cycles appear to use different mechanisms to overcome the energy barrier involved in converting all-trans- to 11-cis-retinoid. Abnormal processing of all-trans-retinal in the rod regeneration cycle leads to retinal degeneration, suggesting that excessive amounts of the retinoid itself or its derivatives are toxic. This line of reasoning led to the development of various approaches to modifying the activity of the rod visual cycle as a possible therapeutic approach to delay or prevent retinal degeneration in inherited retinal diseases and perhaps in the dry form of macular degeneration (geographic atrophy). In spite of great progress in understanding the functioning of rod and cone regeneration cycles at a molecular level, resolution of a number of remaining puzzling issues will offer insight into the amelioration of several blinding retinal diseases.

Keywords

  • Vision
  • Retina
  • Rod
  • Cone
  • Regeneration
  • Visual cycle
  • CRALBP
  • RPE65
  • 11-cis-retinol
  • 11-cis retinal
  • All-trans-retinol
  • All-trans-retinal

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Fig. 9.1
Fig. 9.2
Fig. 9.3

Abbreviations

AAV:

adeno-associated virus

ABCA4:

ATP-binding cassette type 4

AMD:

age-related macular degeneration

A2E:

N-retinylidene-N-retinylethanolamine, a bisretinoid

At-Ral:

all-trans-retinal

At-RE:

all-trans-retinyl ester

At-Rol:

all-trans-retinol

CRABP:

cellular retinoic acid-binding protein

CRALBP:

cellular retinal-binding protein

CRBP1:

cellular retinol-binding protein type 1

DAPI:

4’,6-diamidino-2-phenylindole

IPM:

interphotoreceptor matrix

IRBP:

interphotoreceptor retinoid-binding protein

LCA:

Leber’s congenital amaurosis

MFAT:

multifunctional O-acyltransferase

NHERF1:

sodium hydrogen exchanger regulatory factor type 1

RDH:

retinol dehydrogenase

11-Ral:

11-cis-retinal

11-Rol:

11-cis-retinol

11-RE:

11-cis-retinyl ester

PA:

phosphatidic acid

PC:

phosphatidylcholine

PDZ:

postsynaptic density 95, discs large, ZO1

PE:

phosphatidylethanolamine

PI(3,4,5)P3:

phosphatidylinositol (3,4,5) tris-phosphate

PS:

phosphatidylserine

RalDi:

retinal dimer

RAR:

retinoic acid receptor

RBP:

retinol binding protein

Retinene:

earlier name for retinal

RGR-opsin:

retinal g-protein receptor opsin

RIP1 or −3 kinases:

receptor interacting protein kinases 1 or 3

ROS:

rod outer segments

RPE:

retinal pigment epithelial or epithelium

RPE65:

retinal pigment epithelial protein 65 kDa, aka isomerohydrolase

RXR:

retinoid X-receptor

SUV:

small unilamellar vesicles

TNFα:

tumor necrosis factor α

VCM:

visual cycle modulation

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Acknowledgements

The author acknowledges the support of the Departments of Biochemistry and Ophthalmology at the University of Washington during preparation of this Chapter.

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Saari, J.C. (2016). Vitamin A and Vision. In: Asson-Batres, M., Rochette-Egly, C. (eds) The Biochemistry of Retinoid Signaling II. Subcellular Biochemistry, vol 81. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0945-1_9

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