Selective utilization of serum vitamin A for visual pigment synthesis

1989 ◽  
Vol 142 (1) ◽  
pp. 207-214
Author(s):  
A. T. Tsin ◽  
S. N. Gentles ◽  
E. A. Castillo
Keyword(s):  
Vitamin A ◽  
Visual Pigment ◽  
Carassius Auratus ◽  
High Performance ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Serum Vitamin ◽  
Pigment Synthesis ◽  
Goldfish Carassius Auratus ◽  
Vitamin A2

Two groups of goldfish (Carassius auratus) were subjected to light and temperature conditions known to promote a contrast in their scotopic visual pigment compositions. After 3 weeks, the porphyropsin/rhodopsin ratio in the neuroretina of these goldfish ranged from 99% porphyropsin in one group to 59% in the other. Samples of blood, liver and retinal pigment epithelium (RPE) were also removed from these animals and analysed by high-performance liquid chromatography (HPLC) for vitamin A composition. There was consistently more vitamin A2 than vitamin A1 (over 50% vitamin A2) in both vitamin A alcohol and vitamin A esters extracted from the liver and the RPE. In contrast, only 30% of all vitamin A extracted from the blood was vitamin A2. These observations suggest that it is mainly vitamin A1 that is transported in the blood, whereas vitamin A2 is selectively retained in the liver and in the RPE and used to form porphyropsin in the eye.

The vitamin a transporter STRA6 adjusts the stoichiometry of chromophore and opsins in visual pigment synthesis and recycling

2021 ◽  
Author(s):  
Srinivasagan Ramkumar ◽  
Vipul M Parmar ◽  
Ivy Samuels ◽  
Nathan A Berger ◽  
Beata Jastrzebska ◽  
...  
Keyword(s):  
Vitamin A ◽  
Visual Pigment ◽  
Binding Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinol Binding Protein ◽  
Marker Genes ◽  
Cone Photoreceptors ◽  
Pigment Synthesis ◽  
Deficient Mice

Abstract The retinal pigment epithelium of the vertebrate eyes acquires vitamin A from circulating retinol binding protein for chromophore biosynthesis. The chromophore covalently links with an opsin protein in the adjacent photoreceptors of the retina to form the bipartite visual pigment complexes. We here analyzed visual pigment biosynthesis in mice deficient for the retinol binding protein receptor STRA6. We observed that chromophore content was decreased throughout the life cycle of these animals, indicating that lipoprotein-dependent delivery pathways for the vitamin cannot substitute for STRA6. Changes in the expression of photoreceptor marker genes, including a down-regulation of the genes encoding rod and cone opsins, paralleled the decrease in ocular retinoid concentration in STRA6-deficient mice. Despite this adaptation, cone photoreceptors displayed absent or mislocalized opsins at all ages examined. Rod photoreceptors entrapped the available chromophore but exhibited significant amounts of chromophore-free opsins in the dark-adapted stage. Treatment of mice with pharmacological doses of vitamin A ameliorated the rod phenotype but did not restore visual pigment synthesis in cone photoreceptors of STRA6-deficient mice. The imbalance between chromophore and opsin concentrations of rod and cone photoreceptors was associated with an unfavorable retinal physiology, including diminished electrical responses of photoreceptors to light, and retinal degeneration during aging. Together, our study demonstrates that STRA6 is critical to adjust the stoichiometry of chromophore and opsins in rod cone photoreceptors and to prevent pathologies associated with ocular vitamin A deprivation.

Retinyl esters in the vertebrate neuroretina

1989 ◽  
Vol 256 (1) ◽  
pp. R255-R258 ◽  
Author(s):  
K. A. Rodriguez ◽  
A. T. Tsin
Keyword(s):  
Visual Pigment ◽  
High Performance ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinyl Palmitate ◽  
Visual Pigments ◽  
Pigment Synthesis ◽  
Retinyl Ester ◽  
Retinyl Ester Hydrolase ◽  
Retinyl Esters

High-performance liquid chromatography (HPLC) was employed to measure retinyl esters in the vertebrate retina. Both retina and retinal pigment epithelium (RPE) from frog, chicken, and bovine eyes were studied. In comparison to the RPE, the retina possessed a significant level of 11-cis and all trans retinyl palmitate. Using a sensitive radioassay, we also detected the presence of retinyl ester hydrolase (REH) activity in homogenates prepared from both retina and RPE. The rate of retinyl ester hydrolysis in these retinas was sufficiently high to supply retinal chromophores for the metabolic renewal and for the regeneration of visual pigments. In comparison to retinyl esters in the RPE, retinyl esters in the retina are located much closer to the sites of visual pigment synthesis and regeneration. Hence it is possible that these retinyl esters play a more important role in the visual cycle than those in the RPE.

scholarly journals Peropsin, a novel visual pigment-like protein located in the apical microvilli of the retinal pigment epithelium

1997 ◽  
Vol 94 (18) ◽  
pp. 9893-9898 ◽  
Author(s):  
H. Sun ◽  
D. J. Gilbert ◽  
N. G. Copeland ◽  
N. A. Jenkins ◽  
J. Nathans
Keyword(s):  
Retinal Pigment Epithelium ◽  
Visual Pigment ◽  
Pigment Epithelium ◽  
Retinal Pigment

scholarly journals Peropsin modulates transit of vitamin A from retina to retinal pigment epithelium

2017 ◽  
Vol 292 (52) ◽  
pp. 21407-21416 ◽  
Author(s):  
Jeremy D. Cook ◽  
Sze Yin Ng ◽  
Marcia Lloyd ◽  
Shannan Eddington ◽  
Hui Sun ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Vitamin A ◽  
Pigment Epithelium ◽  
Retinal Pigment

scholarly journals Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 554
Author(s):  
Laura Hellinen ◽  
Sina Bahrpeyma ◽  
Anna-Kaisa Rimpelä ◽  
Marja Hagström ◽  
Mika Reinisalo ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Performance ◽  
Dissociation Constants ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Binding Study ◽  
Penicillin G ◽  
Label Free ◽  
Microscale Thermophoresis ◽  
Melanin Binding

Interactions between drugs and melanin pigment may have major impacts on pharmacokinetics. Therefore, melanin binding can modify the efficacy and toxicity of medications in ophthalmic and other disease of pigmented tissues, such as melanoma. As melanin is present in many pigmented tissues in the human body, investigation of pigment binding is relevant in drug discovery and development. Conventionally, melanin binding assays have been performed using an equilibrium binding study followed by chemical analytics, such as LC/MS. This approach is laborious, relatively slow, and limited to facilities with high performance quantitation instrumentation. We present here a screening of melanin binding with label-free microscale thermophoresis (MST) that utilizes the natural autofluorescence of melanin. We determined equilibrium dissociation constants (Kd) of 11 model compounds with melanin nanoparticles. MST categorized the compounds into extreme (chloroquine, penicillin G), high (papaverine, levofloxacin, terazosin), intermediate (timolol, nadolol, quinidine, propranolol), and low melanin binders (atropine, methotrexate, diclofenac) and displayed good correlation with binding parameter values obtained with the conventional binding study and LC/MS analytics. Further, correlation was seen between predicted melanin binding in human retinal pigment epithelium and choroid (RPE-choroid) and Kd values obtained with MST. This method represents a useful and fast approach for classification of compounds regarding melanin binding. Thus, the method can be utilized in various fields, including drug discovery, pharmacokinetics, and toxicology.

scholarly journals Effect of Storage Temperature on Key Functions of Cultured Retinal Pigment Epithelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lara Pasovic ◽  
Jon Roger Eidet ◽  
Berit S. Brusletto ◽  
Torstein Lyberg ◽  
Tor P. Utheim
Keyword(s):  
Tight Junctions ◽  
Dna Microarrays ◽  
Storage Temperature ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Pcr Analysis ◽  
Pigment Synthesis ◽  
Expression Levels ◽  
Microarray Expression

Purpose. Replacement of the diseased retinal pigment epithelium (RPE) with cells capable of performing the specialized functions of the RPE is the aim of cell replacement therapy for treatment of macular degenerative diseases. A storage method for RPE is likely to become a prerequisite for the establishment of such treatment. Herein, we analyze the effect of storage temperature on key functions of cultured RPE cells.Methods. Cultured ARPE-19 cells were stored in Minimum Essential Medium at 4°C, 16°C, and 37°C for seven days. Total RNA was isolated and the gene expression profile was determined using DNA microarrays. Comparison of the microarray expression values with qRT-PCR analysis of selected genes validated the results.Results. Expression levels of several key genes involved in phagocytosis, pigment synthesis, the visual cycle, adherens, and tight junctions, and glucose and ion transport were maintained close to control levels in cultures stored at 4°C and 16°C. Cultures stored at 37°C displayed regulational changes in a larger subset of genes related to phagocytosis, adherens, and tight junctions.Conclusion. RPE cultures stored at 4°C and 16°C for one week are capable of maintaining the expression levels of genes important for key RPE functions close to control levels.

scholarly journals Vitamin A aldehyde-taurine adduct and the visual cycle

2020 ◽  
Vol 117 (40) ◽  
pp. 24867-24875
Author(s):  
Hye Jin Kim ◽  
Jin Zhao ◽  
Janet R. Sparrow
Keyword(s):  
Schiff Base ◽  
Vitamin A ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Photoreceptor Cells ◽  
Light Sensitivity ◽  
Retinal Pigment Epithelial Cells ◽  
Photon Absorption ◽  
Visual Cycle ◽  
Covalently Linked

Visual pigment consists of opsin covalently linked to the vitamin A-derived chromophore, 11-cis-retinaldehyde. Photon absorption causes the chromophore to isomerize from the 11-cis- to all-trans-retinal configuration. Continued light sensitivity necessitates the regeneration of 11-cis-retinal via a series of enzyme-catalyzed steps within the visual cycle. During this process, vitamin A aldehyde is shepherded within photoreceptors and retinal pigment epithelial cells to facilitate retinoid trafficking, to prevent nonspecific reactivity, and to conserve the 11-cis configuration. Here we show that redundancy in this system is provided by a protonated Schiff base adduct of retinaldehyde and taurine (A1-taurine, A1T) that forms reversibly by nonenzymatic reaction. A1T was present as 9-cis, 11-cis, 13-cis, and all-trans isomers, and the total levels were higher in neural retina than in retinal pigment epithelium (RPE). A1T was also more abundant under conditions in which 11-cis-retinaldehyde was higher; this included black versus albino mice, dark-adapted versus light-adapted mice, and mice carrying the Rpe65-Leu450 versus Rpe65-450Met variant. Taurine levels paralleled these differences in A1T. Moreover, A1T was substantially reduced in mice deficient in the Rpe65 isomerase and in mice deficient in cellular retinaldehyde-binding protein; in these models the production of 11-cis-retinal is compromised. A1T is an amphiphilic small molecule that may represent a mechanism for escorting retinaldehyde. The transient Schiff base conjugate that the primary amine of taurine forms with retinaldehyde would readily hydrolyze to release the retinoid and thus may embody a pool of 11-cis-retinal that can be marshalled in photoreceptor cells.

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