Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus

10.1038/9707 ◽  
1999 ◽  
Vol 22 (2) ◽  
pp. 188-191 ◽  
Author(s):  
Hiroyuki Yamamoto ◽  
András Simon ◽  
Ulf Eriksson ◽  
Eddie Harris ◽  
Eliot L. Berson ◽  
...  
Keyword(s):  
Dark Adaptation ◽  
Retinol Dehydrogenase ◽  
Gene Encoding ◽  
Fundus Albipunctatus

scholarly journals Disruption of the 11-cis-Retinol Dehydrogenase Gene Leads to Accumulation of cis-Retinols andcis-Retinyl Esters

2000 ◽  
Vol 20 (12) ◽  
pp. 4275-4287 ◽  
Author(s):  
Carola A. G. G. Driessen ◽  
Huub J. Winkens ◽  
Kirstin Hoffmann ◽  
Leonoor D. Kuhlmann ◽  
Bert P. M. Janssen ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Dehydrogenase Activity ◽  
Knockout Mice ◽  
Dark Adaptation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinol Dehydrogenase ◽  
Retinyl Ester ◽  
Fundus Albipunctatus ◽  
Dehydrogenase Gene

ABSTRACT To elucidate the possible role of 11-cis-retinol dehydrogenase in the visual cycle and/or 9-cis-retinoic acid biosynthesis, we generated mice carrying a targeted disruption of the 11-cis-retinol dehydrogenase gene. Homozygous 11-cis-retinol dehydrogenase mutants developed normally, including their retinas. There was no appreciable loss of photoreceptors. Recently, mutations in the 11-cis-retinol dehydrogenase gene in humans have been associated with fundus albipunctatus. In 11-cis-retinol dehydrogenase knockout mice, the appearance of the fundus was normal and punctata typical of this human hereditary ocular disease were not present. A second typical symptom associated with this disease is delayed dark adaptation. Homozygous 11-cis-retinol dehydrogenase mutants showed normal rod and cone responses. 11-cis-Retinol dehydrogenase knockout mice were capable of dark adaptation. At bleaching levels under which patients suffering from fundus albipunctatus could be detected unequivocally, 11-cis-retinol dehydrogenase knockout animals displayed normal dark adaptation kinetics. However, at high bleaching levels, delayed dark adaptation in 11-cis-retinol dehydrogenase knockout mice was noticed. Reduced 11-cis-retinol oxidation capacity resulted in 11-cis-retinol/13-cis-retinol and 11-cis-retinyl/13-cis-retinyl ester accumulation. Compared with wild-type mice, a large increase in the 11-cis-retinyl ester concentration was noticed in 11-cis-retinol dehydrogenase knockout mice. In the murine retinal pigment epithelium, there has to be an additional mechanism for the biosynthesis of 11-cis-retinal which partially compensates for the loss of the 11-cis-retinol dehydrogenase activity. 11-cis-Retinyl ester formation is an important part of this adaptation process. Functional consequences of the loss of 11-cis-retinol dehydrogenase activity illustrate important differences in the compensation mechanisms between mice and humans. We furthermore demonstrate that upon 11-cis-retinol accumulation, the 13-cis-retinol concentration also increases. This retinoid is inapplicable to the visual processes, and we therefore speculate that it could be an important catabolic metabolite and its biosynthesis could be part of a process involved in regulating 11-cis-retinol concentrations within the retinal pigment epithelium of 11-cis-retinol dehydrogenase knockout mice.

scholarly journals Delayed Dark Adaptation in 11-cis-Retinol Dehydrogenase-deficient Mice

2005 ◽  
Vol 280 (10) ◽  
pp. 8694-8704 ◽  
Author(s):  
Tom S. Kim ◽  
Akiko Maeda ◽  
Tadao Maeda ◽  
Cynthia Heinlein ◽  
Natalia Kedishvili ◽  
...  
Keyword(s):  
Dark Adaptation ◽  
Retinol Dehydrogenase ◽  
Deficient Mice

scholarly journals Biallelic inheritance in a single Pakistani family with intellectual disability implicates new candidate gene RDH14

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephen F. Pastore ◽  
Tahir Muhammad ◽  
Ricardo Harripaul ◽  
Rebecca Lau ◽  
Muhammad Tariq Masood Khan ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Autosomal Recessive ◽  
Ion Homeostasis ◽  
Cerebellar Atrophy ◽  
Chloride Ion ◽  
Hek293 Cells ◽  
Retinol Dehydrogenase ◽  
Gene Encoding ◽  
Whole Exome ◽  
Transcription Data

AbstractIn a multi-branch family from Pakistan, individuals presenting with palmoplantar keratoderma segregate in autosomal dominant fashion, and individuals with intellectual disability (ID) segregate in apparent autosomal recessive fashion. Initial attempts to identify the ID locus using homozygosity-by-descent (HBD) mapping were unsuccessful. However, following an assumption of locus heterogeneity, a reiterative HBD approach in concert with whole exome sequencing (WES) was employed. We identified a known disease-linked mutation in the polymicrogyria gene, ADGRG1, in two affected members. In the remaining two (living) affected members, HBD mapping cross-referenced with WES data identified a single biallelic frameshifting variant in the gene encoding retinol dehydrogenase 14 (RDH14). Transcription data indicate that RDH14 is expressed in brain, but not in retina. Magnetic resonance imaging for the individuals with this RDH14 mutation show no signs of polymicrogyria, however cerebellar atrophy was a notable feature. RDH14 in HEK293 cells localized mainly in the nucleoplasm. Co-immunoprecipitation studies confirmed binding to the proton-activated chloride channel 1 (PACC1/TMEM206), which is greatly diminished by the mutation. Our studies suggest RDH14 as a candidate for autosomal recessive ID and cerebellar atrophy, implicating either disrupted retinoic acid signaling, or, through PACC1, disrupted chloride ion homeostasis in the brain as a putative disease mechanism.

scholarly journals Biochemical Defects in 11-cis-Retinol Dehydrogenase Mutants Associated with Fundus Albipunctatus

2001 ◽  
Vol 276 (52) ◽  
pp. 49251-49257 ◽  
Author(s):  
Martin Lidén ◽  
Anna Romert ◽  
Kristian Tryggvason ◽  
Bengt Persson ◽  
Ulf Eriksson
Keyword(s):  
Retinol Dehydrogenase ◽  
Fundus Albipunctatus

scholarly journals Function of mammalian M-cones depends on the level of CRALBP in Müller cells

2020 ◽  
Vol 153 (1) ◽  
Author(s):  
Alexander V. Kolesnikov ◽  
Philip D. Kiser ◽  
Krzysztof Palczewski ◽  
Vladimir J. Kefalov
Keyword(s):  
Dark Adaptation ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Müller Cells ◽  
Muller Cells ◽  
Visual Cycle ◽  
Gene Encoding ◽  
Rods And Cones ◽  
Cone Pigment

Cone photoreceptors mediate daytime vision in vertebrates. The rapid and efficient regeneration of their visual pigments following photoactivation is critical for the cones to remain photoresponsive in bright and rapidly changing light conditions. Cone pigment regeneration depends on the recycling of visual chromophore, which takes place via the canonical visual cycle in the retinal pigment epithelium (RPE) and the Müller cell–driven intraretinal visual cycle. The molecular mechanisms that enable the neural retina to regenerate visual chromophore for cones have not been fully elucidated. However, one known component of the two visual cycles is the cellular retinaldehyde-binding protein (CRALBP), which is expressed both in the RPE and in Müller cells. To understand the significance of CRALBP in cone pigment regeneration, we examined the function of cones in mice heterozygous for Rlbp1, the gene encoding CRALBP. We found that CRALBP expression was reduced by ∼50% in both the RPE and retina of Rlbp1+/− mice. Electroretinography (ERG) showed that the dark adaptation of rods and cones is unaltered in Rlbp1+/− mice, indicating a normal RPE visual cycle. However, pharmacologic blockade of the RPE visual cycle revealed suppressed cone dark adaptation in Rlbp1+/− mice in comparison with controls. We conclude that the expression level of CRALPB specifically in the Müller cells modulates the efficiency of the retina visual cycle. Finally, blocking the RPE visual cycle also suppressed further cone dark adaptation in Rlbp1−/− mice, revealing a shunt in the classical RPE visual cycle that bypasses CRALBP and allows partial but unexpectedly rapid cone dark adaptation.

scholarly journals Retinol dehydrogenase 8 and ATP-binding cassette transporter 4 modulate dark adaptation of M-cones in mammalian retina

2015 ◽  
Vol 593 (22) ◽  
pp. 4923-4941 ◽  
Author(s):  
Alexander V. Kolesnikov ◽  
Akiko Maeda ◽  
Peter H. Tang ◽  
Yoshikazu Imanishi ◽  
Krzysztof Palczewski ◽  
...  
Keyword(s):  
Dark Adaptation ◽  
Atp Binding ◽  
Retinol Dehydrogenase ◽  
Atp Binding Cassette Transporter ◽  
Mammalian Retina ◽  
Atp Binding Cassette

XRF and PIXE Analysis of light and Dark Adapted Ocular Tissue

1982 ◽  
Vol 40 ◽  
pp. 190-191
Author(s):  
B. J. Panessa ◽  
H. W. Kraner ◽  
J. B. Warren ◽  
K. W. Jones
Keyword(s):  
Trace Metals ◽  
Pigment Epithelium ◽  
Nerve Impulse ◽  
Light Response ◽  
Ocular Tissue ◽  
Emission Spectrometry ◽  
Retinol Dehydrogenase ◽  
Pixe Analysis ◽  
X Ray ◽  
Optimal Function

During photoexcitation the retina requires specific electrolytes and trace metals for optimal function (Na, Mg, Cl, K, Ca, S, P, Cu and Zn). According to Hagins (1981), photoexcitation and generation of a nerve impulse involves the movement of Ca from the rhodopsin-ladened membranes of the rod outer segment (ROS) to the plasmalemma, which in turn decreases the in-flow of Na into the photoreceptor, resulting in hyperpolarization. In toad isolated retinas, the presence of Ba has been found to increase the amplitude and prolong the delay of the light response (Brown and Flaming, 1978). Trace metals such as Cu, Zn and Se are essential for the activity of the metalloenzymes of the retina and retina pigment epithelium (RPE) (i.e. carbonic anhydrase, retinol dehydrogenase, tyrosinase, glutathione peroxidase, superoxide dismutase...). Therefore the content and fluctuations of these elements in the retina and choroid are of fundamental importance for the maintenance of vision. This paper presents elemental data from light and dark adapted frog ocular tissues examined by electron beam induced x-ray microanalysis, x-ray fluorescence spectrometry (XRF) and proton induced x-ray emission spectrometry (PIXE).

B-Vitamins, Methylenetetrahydrofolate Reductase (MTHFR) and Hypertension

2011 ◽  
Vol 81 (4) ◽  
pp. 240-244 ◽  
Author(s):  
Mary Ward ◽  
Carol P Wilson ◽  
J J Strain ◽  
Geraldine Horigan ◽  
John M. Scott ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Low Dose ◽  
Methylenetetrahydrofolate Reductase ◽  
Genetic Determinant ◽  
Gene Encoding ◽  
Homocysteine Concentration ◽  
Homozygous Mutant ◽  
B Vitamin

Hypertension is a leading risk factor for cardiovascular disease (CVD) and stroke. A common polymorphism in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR), previously identified as the main genetic determinant of elevated homocysteine concentration and also recognized as a risk factor for CVD, appears to be independently associated with hypertension. The B-vitamin riboflavin is required as a cofactor by MTHFR and recent evidence suggests it may have a role in modulating blood pressure, specifically in those with the homozygous mutant MTHFR 677 TT genotype. If studies confirm that this genetic predisposition to hypertension is correctable by low-dose riboflavin, the findings could have important implications for the management of hypertension given that the frequency of this polymorphism ranges from 3 to 32 % worldwide.

Identification of a single-copy gene encoding a Type I chlorophyll a/b-binding polypeptide of photosystem I in Arabidopsis thaliana

1992 ◽  
Vol 84 (4) ◽  
pp. 561-567 ◽  
Author(s):  
Poul E. Jensen ◽  
Michael Kristensen ◽  
Tine Hoff ◽  
Jan Lehmbeck ◽  
Bjarne M. Stummann ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Chlorophyll A ◽  
Photosystem I ◽  
Single Copy ◽  
Type I ◽  
Single Copy Gene ◽  
Gene Encoding ◽  
Copy Gene
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