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

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.

Download Full-text

Selective utilization of serum vitamin A for visual pigment synthesis

Journal of Experimental Biology ◽

10.1242/jeb.142.1.207 ◽

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.

Download Full-text

Endocytosis and degradation of interstitial retinol-binding protein: differential capabilities of cells that border the interphotoreceptor matrix.

The Journal of Cell Biology ◽

10.1083/jcb.100.5.1676 ◽

1985 ◽

Vol 100 (5) ◽

pp. 1676-1681 ◽

Cited By ~ 25

Author(s):

J G Hollyfield ◽

H H Varner ◽

M E Rayborn ◽

G I Liou ◽

C D Bridges

Keyword(s):

Acid Phosphatase ◽

Binding Protein ◽

Pigment Epithelium ◽

Retinol Binding Protein ◽

Apical Plasma Membrane ◽

Multivesicular Bodies ◽

Cone Photoreceptors ◽

Interphotoreceptor Matrix ◽

Rod And Cone Photoreceptors

Between the pigment epithelium and the outer limiting membrane of the retina is an extracellular compartment filled with the interphotoreceptor matrix (IPM). A prominent component of the IPM is a glycoprotein known as interstitial retinol-binding protein (IRBP). Using in vitro techniques, we compared the ability of the cells that border this compartment to internalize colloidal gold (CG) coated with either IRBP or ovalbumin, a glycoprotein not found in the IPM. Neither IRBP-CG nor ovalbumin-CG was internalized by the Muller's cells. Both rod and cone photoreceptors take up IRBP-CG, which is observed in small vesicles and multivesicular bodies. Neither photoreceptor type takes up ovalbumin-CG. Acid phosphatase cytochemistry indicates that acid phosphatase reaction product in the multivesicular bodies co-localizes with IRBP-CG, which suggests that this molecule is degraded by rod and cone photoreceptors and is not recycled. The pigment epithelium internalizes IRBP-CG and ovalbumin-CG, both of which remain in small cytoplasmic vesicles near the apical plasma membrane. There is no indication that vesicles that contain either IRBP-CG or ovalbumin-CG fuse with the lysosomal system in the pigment epithelial cells during the incubation.

Download Full-text

Retinyl esters in the vertebrate neuroretina

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.1.r255 ◽

1989 ◽

Vol 256 (1) ◽

pp. R255-R258 ◽

Cited By ~ 2

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.

Download Full-text