Vitamin a in Eye Tissues

Wald, George

doi:10.1085/jgp.18.6.905

Cited by 101 publications

(16 citation statements)

References 10 publications

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“…Its mechanism of action was elucidated by the work of many researchers over a period of more than a century (2)(3)(4). In fact, the last landmark discovery in visual photoreception was the cloning of human genes encoding the blue, green, and red opsins in 1986 (5).…”

Section: Historical Perspectivementioning

confidence: 99%

Cryptochrome: The Second Photoactive Pigment in the Eye and Its Role in Circadian Photoreception

Sancar

2000

Annu. Rev. Biochem.

243

201

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Key Words blue-light photoreceptor, flavoprotein, retina, suprachiasmatic nucleus, circadian blind mice, seasonal affective disorder s Abstract Circadian rhythms are oscillations in the biochemical, physiological, and behavioral functions of organisms that occur with a periodicity of approximately 24 h. They are generated by a molecular clock that is synchronized with the solar day by environmental photic input. The cryptochromes are the mammalian circadian photoreceptors. They absorb light and transmit the electromagnetic signal to the molecular clock using a pterin and flavin adenine dinucleotide (FAD) as chromophore/cofactors, and are evolutionarily conserved and structurally related to the DNA repair enzyme photolyase. Humans and mice have two cryptochrome genes, CRY1 and CRY2, that are differentially expressed in the retina relative to the opsin-based visual photoreceptors. CRY1 is highly expressed with circadian periodicity in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). Mutant mice lacking either Cry1 or Cry2 have impaired light induction of the clock gene mPer1 and have abnormally short or long intrinsic periods, respectively. The double mutant has normal vision but is defective in mPer1 induction by light and lacks molecular and behavioral rhythmicity in constant darkness. Thus, cryptochromes are photoreceptors and central components of the molecular clock. Genetic evidence also shows that cryptochromes are circadian photoreceptors in Drosophila and Arabidopsis, raising the possibility that they may be universal circadian photoreceptors. Research on cryptochromes may provide new understanding of human diseases such as seasonal affective disorder and delayed sleep phase syndrome. CONTENTS

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Section: Historical Perspectivementioning

confidence: 99%

Cryptochrome: The Second Photoactive Pigment in the Eye and Its Role in Circadian Photoreception

Sancar

2000

Annu. Rev. Biochem.

243

201

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“…The all-trans-retinal dissociates from opsin in a series of steps called photo-bleaching. The final stage is conversion of 11-cis-retinal rebind to opsin to reform rhodopsin in the retina [15][16][17] . Kuhne showed that rhodopsin in the retina is only regenerated when the retina is attached to retinal pigmented epithelium (RPE) 17 .…”

Section: Vision Cyclementioning

confidence: 99%

Vitamin A, Retinoic Acid and Tamibarotene, a Front Toward Its Advances: A Review

Zhu

Al-kaf

2019

Univ J Pharm Res

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Vitamin A and its derivative retinoic acid (13-cis RA, 9-cis RA, all-trans RA) and recent tamibarotene have been shown a broad variety of biological actives in human, such as vision, embryonic development, cell growth and cellular differentiation and immune function. These precise functions of RA are mediated by their retinoic acid receptors (RARs). In the past five decades, retinoic acid (RA) proved therapeutic benefits in cancer prevention, in skin diseases and in acute promyelocytic leukemia (APL).The elucidation of the molecular basis of vitamin A acid and its retinoid pharmacology in APL has been illustrated in several publications, the detail molecular model of gene regulation had also been proposed by Zhu in earlier 90s. A molecular model is further revised. As an approach to APL treatment, one possible the action of retinoic acid (RA), A consensus sequence (TCAGGTCA motif ) has been postulated for thyroid hormone (TRE) and retinoic acid responsive element (RARE)-containing in the promoter region of target genes. High dose of RA-RARE-PML/RARa complexes in intracellular localization appears to relieve repressors from DNA-bound receptor, including the dissociation of co-re pressor complexes N-CoR, SMRT and HDACs from PML-RARa or PML-RARa/RXR. Also release PML/RARa -mediated transcription repression. This transcriptional derepression occurs at RARa target gene promoter. Consequentially, PML-RARa chimera converted receptor from a repressor to a RA-dependent activator of transcription. The resulting pml-RARA oncoprotein proteolytic degradation occurs through the autophagy-lysosome pathway and the ubiquitin SUMO-proteasome system(UPS) as well as caspase 3, or lysosomal protease (cathepsin D) enzyme or/and EI-like ubiquitin-activating enzyme(UBEIL) induction. Accordingly the expression level of PML-RARa downregulated. PML protein relocalizes into the wild-type nuclear body (PML-NB) configuration or a truncated PML-RARa fusion fragment detected or/and the wild-type RAR upregulated. An effect is to relieve the blockade of pml/RARa-mediated RA dependent promyelocytic differentiation, and retinoic acid (9-cid RA,ATRA, Am80) in APL therapy. Here, oncogenic pml/RARa as constitutive transcriptional repressor that block myeloid differentiation at promyelocytic phenotype. RA can overcome the transcrptional repressor activity of pml/RARa. The oncogenic pml/RARa uncovers a pathogenic role in leukemogenesis of APL through blocking promyelocytic differentiation. This oncogenic receptor derivative pml/ RARa chimera is locked in their "off" regular mode thereby constitutively repressing transcription of target genes or key enzymes (such as AP-1, PTEN, DAPK2,UP.1, p21WAF/CCKN1A）that are critical for differentiation of hematopoietic cells. This is first described in eukaryotes.

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“…Another shared feature among the animal kingdom is the ability for all visual pigments to signal multiple light events. This continued transduction depends on the regeneration of the visual chromophore 1‐4 . In the vertebrate retina, the re‐isomerization of at‐RAL to 11c‐RAL occurs in the retinal pigment epithelium (RPE), a monolayer of cells directly adjacent to the photoreceptors, in a process known as the visual (retinoid) cycle 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Single particle cryo‐EM of the complex between interphotoreceptor retinoid‐binding protein and a monoclonal antibody

Sears

Albiez

Gulati³

et al. 2020

FASEB j.

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Interphotoreceptor retinoid‐binding protein (IRBP) is a highly expressed protein secreted by rod and cone photoreceptors that has major roles in photoreceptor homeostasis as well as retinoid and polyunsaturated fatty acid transport between the neural retina and retinal pigment epithelium. Despite two crystal structures reported on fragments of IRBP and decades of research, the overall structure of IRBP and function within the visual cycle remain unsolved. Here, we studied the structure of native bovine IRBP in complex with a monoclonal antibody (mAb5) by cryo‐electron microscopy, revealing the tertiary and quaternary structure at sufficient resolution to clearly identify the complex components. Complementary mass spectrometry experiments revealed the structure and locations of N‐linked carbohydrate post‐translational modifications. This work provides insight into the structure of IRBP, displaying an elongated, flexible three‐dimensional architecture not seen among other retinoid‐binding proteins. This work is the first step in elucidation of the function of this enigmatic protein.

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Vitamin a in Eye Tissues

Cited by 101 publications

References 10 publications

Cryptochrome: The Second Photoactive Pigment in the Eye and Its Role in Circadian Photoreception

Cryptochrome: The Second Photoactive Pigment in the Eye and Its Role in Circadian Photoreception

Vitamin A, Retinoic Acid and Tamibarotene, a Front Toward Its Advances: A Review

Single particle cryo‐EM of the complex between interphotoreceptor retinoid‐binding protein and a monoclonal antibody

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