scholarly journals Retinoids in the visual cycle: Role of the retinal G protein-coupled receptor

2020 ◽  
pp. jlr.TR120000850 ◽  
Author(s):  
Elliot H Choi ◽  
Anahita Daruwalla ◽  
Susie Suh ◽  
Henri Leinonen ◽  
Krzysztof Palczewski
Keyword(s):  
G Protein ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Light Sensitivity ◽  
Visual Signal ◽  
Enzymatic Reactions ◽  
Visual Cycle ◽  
Retinal Regeneration ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

Driven by the energy of a photon, the visual pigments in rod and cone photoreceptor cells isomerize 11-cis-retinal to the all-trans configuration. This photochemical reaction initiates the signal transduction pathway that eventually leads to the transmission of a visual signal to the brain and leaves the opsins insensitive to further light stimulation. For the eye to restore light sensitivity, opsins require recharging with 11-cis-retinal. This trans–cis back conversion is achieved through a series of enzymatic reactions composing the retinoid (visual) cycle. Although it is evident that the classical retinoid cycle is critical for vision, the existence of an adjunct pathway for 11-cis-retinal regeneration has been debated for many years. Retinal pigment epithelium (RPE)–retinal G protein-coupled receptor (RGR) has been identified previously as a mammalian retinaldehyde photoisomerase homologous to retinochrome found in invertebrates. Using pharmacological, genetic, and biochemical approaches, researchers have now established the physiological relevance of the RGR in 11-cis-retinal regeneration. The photoisomerase activity of RGR in the RPE and Müller glia explains how the eye can remain responsive in daylight. In this review, we will focus on retinoid metabolism in the eye and visual chromophore regeneration mediated by RGR.  

scholarly journals A G-Protein Coupled Receptor and Macular Degeneration

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 910
Author(s):  
Anna G. Figueroa ◽  
Brian S. McKay
Keyword(s):  
Macular Degeneration ◽  
G Protein ◽  
Racial Bias ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
G Protein Coupled Receptor ◽  
Primary Defect ◽  
Age Related ◽  
G Protein Coupled

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. The risk of AMD increases with age and is most common among the white population. Here, we discuss the convergence of factors related to race, pigmentation, and susceptibility to AMD, where the primary defect occurs in retinal support cells, the retinal pigment epithelium (RPE). We explore whether the observed racial bias in AMD incidence is related to innate differences in the basal level of pigmentation between races, and whether the pigmentation pathway activity in the RPE might protect from retinal degeneration. More specifically, we explore whether the downstream signaling activity of GPR143, a G-protein coupled receptor in the pigmentation pathway, might underly the racial bias of AMD and be a target to prevent the disease. Lastly, we summarize the past findings of a large retrospective study that investigated the relationship between the stimulation of GPR143 with L-DOPA, the pigmentation pathway, and AMD, to potentially help develop new ways to prevent or treat AMD. The reader of this review will come to understand the racial bias of AMD, which is related to the function of the RPE.

scholarly journals Pathophysiological features of the visual cycle, cascade and metabolic pathways in retinitis pigmentosa

2021 ◽  
Vol 14 (1) ◽  
pp. 80-88
Author(s):  
M. E. Weener ◽  
D. S. Atarshchikov ◽  
V. V. Kadyshev ◽  
I. V. Zolnikova ◽  
A. M. Demchinsky ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Literature Review ◽  
Retinitis Pigmentosa ◽  
Metabolic Pathways ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Visual Signal ◽  
Visual Cycle ◽  
Target Treatment ◽  
Interphotoreceptor Matrix

This literature review offers a detailed description of the genes and proteins involved in pathophysiological processes in isolated retinitis pigmentosa (RP). To date, 84 genes and 7 candidate genes have been described for non-syndromic RP. Each of these genes encodes a protein that plays a role in vital processes in the retina and / or retinal pigment epithelium, including the cascade of phototransduction (transmission of the visual signal), the visual cycle, ciliary transport, the environment of photoreceptor cilia and the interphotoreceptor matrix. The identification and study of pathophysiological pathways affected in non-syndromic RP is important for understanding the main pathogenic ways and developing approaches to target treatment.

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.

scholarly journals G protein–coupled receptors differentially regulate glycosylation and activity of the inwardly rectifying potassium channel Kir7.1

2018 ◽  
Vol 293 (46) ◽  
pp. 17739-17753 ◽  
Author(s):  
Sheridan J. Carrington ◽  
Ciria C. Hernandez ◽  
Daniel R. Swale ◽  
Oluwatosin A. Aluko ◽  
Jerod S. Denton ◽  
...  
Keyword(s):  
Potassium Channel ◽  
G Protein ◽  
Single Channel ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
G Protein Coupled Receptors ◽  
Open Probability ◽  
Inwardly Rectifying Potassium Channel ◽  
Inwardly Rectifying ◽  
G Protein Coupled

Kir7.1 is an inwardly rectifying potassium channel with important roles in the regulation of the membrane potential in retinal pigment epithelium, uterine smooth muscle, and hypothalamic neurons. Regulation of G protein–coupled inwardly rectifying potassium (GIRK) channels by G protein–coupled receptors (GPCRs) via the G protein βγ subunits has been well characterized. However, how Kir channels are regulated is incompletely understood. We report here that Kir7.1 is also regulated by GPCRs, but through a different mechanism. Using Western blotting analysis, we observed that multiple GPCRs tested caused a striking reduction in the complex glycosylation of Kir7.1. Further, GPCR-mediated reduction of Kir7.1 glycosylation in HEK293T cells did not alter its expression at the cell surface but decreased channel activity. Of note, mutagenesis of the sole Kir7.1 glycosylation site reduced conductance and open probability, as indicated by single-channel recording. Additionally, we report that the L241P mutation of Kir7.1 associated with Lebers congenital amaurosis (LCA), an inherited retinal degenerative disease, has significantly reduced complex glycosylation. Collectively, these results suggest that Kir7.1 channel glycosylation is essential for function, and this activity within cells is suppressed by most GPCRs. The melanocortin-4 receptor (MC4R), a GPCR previously reported to induce ligand-regulated activity of this channel, is the only GPCR tested that does not have this effect on Kir7.1.

The Visual Cycle in the Inner Retina of Chicken and the Involvement of Retinal G-Protein-Coupled Receptor (RGR)

2016 ◽  
Vol 54 (4) ◽  
pp. 2507-2517 ◽  
Author(s):  
Nicolás M. Díaz ◽  
Luis P. Morera ◽  
Tomas Tempesti ◽  
Mario E. Guido
Keyword(s):  
G Protein ◽  
Visual Cycle ◽  
G Protein Coupled Receptor ◽  
Inner Retina ◽  
G Protein Coupled
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