Retinal G-protein-coupled receptor deletion exacerbates AMD-like changes via the PINK1-parkin pathway under oxidative stress.

The intake of high dietary fat has been correlated with the progression of age-related macular degeneration (AMD), affecting the function of the retinal pigment epithelium through oxidative stress. A high-fat diet (HFD) can lead to lipid metabolism disorders, excessive production of circulating free fatty acids, and systemic inflammation by aggravating the degree of oxidative stress. Deletion of the retinal G-protein-coupled receptor (RGR-d) has been identified in drusen.

Proteopathy Linked to Exon-Skipping Isoform of RGR-Opsin Contributes to the Pathogenesis of Age-Related Macular Degeneration.

Purpose: Proteopathy is believed to contribute to age-related macular degeneration (AMD). Much research indicates that AMD begins in the retinal pigment epithelium (RPE), which is associated with formation of extracellular drusen, a clinical hallmark of AMD. Human RPE produces a drusen-associated abnormal protein, the exon Ⅵ-skipping splice isoform of retinal G protein-coupled receptor (RGR-d).

Human RGR Gene and Associated Features of Age-Related Macular Degeneration in Models of Retina-Choriocapillaris Atrophy.

Age-related macular degeneration (AMD) is a progressive eye disease and the most common cause of blindness among the elderly. AMD is characterized by early atrophy of the choriocapillaris and retinal pigment epithelium (RPE). Although AMD is a multifactorial disease with many environmental and genetic risk factors, a hallmark of the disease is the origination of extracellular deposits, or drusen, between the RPE and Bruch membrane.

Coexpression of nonvisual opsin, retinal G protein-coupled receptor, and visual pigments in human and bovine cone photoreceptors.

Purpose: Retinal G protein-coupled receptor (RGR) mRNA is transcribed in the outer nuclear layer of human retinas; however, it is not known whether the gene is expressed in the rod or cone photoreceptors. In this study, we investigate broader expression of the normal RGR isoform in photoreceptors of human and bovine retinas.

Methods: We produced and validated a rabbit polyclonal antipeptide antibody (DE15) that is directed against a peptide sequence (SSLLRRWPHGSEGC) partly conserved in RGR across several species.

Targeting of exon VI-skipping human RGR-opsin to the plasma membrane of pigment epithelium and co-localization with terminal complement complex C5b-9.

Purpose: Rare mutations in the human RGR gene lead to autosomal recessive retinitis pigmentosa or dominantly inherited peripapillary choroidal atrophy. Here, we analyze a common exon-skipping isoform of the human retinal G protein-coupled receptor opsin (RGR-d) to determine differences in subcellular targeting between RGR-d and normal RGR and possible association with abnormal traits in the human eye.

Methods: The terminal complement complex (C5b-9), vitronectin, CD46, syntaxin-4, and RGR-d were analyzed in human eye tissue from young and old donors or in cultured fetal RPE cells by means of immunofluorescent labeling and high-resolution confocal microscopy or immunohistochemical staining.

Accumulation of extracellular RGR-d in Bruch's membrane and close association with drusen at intercapillary regions.

Human retinal pigment epithelial (RPE) cells synthesize an extraneous splice isoform of retinal G protein-coupled receptor (RGR). In this study, we analyzed the exon-skipping variant of RGR (RGR-d) that is found in extracellular deposits. RPE-choroid tissue sections were prepared from postmortem human eyes from donors of various ages.

Deposition of exon-skipping splice isoform of human retinal G protein-coupled receptor from retinal pigment epithelium into Bruch's membrane.

Purpose: Human retina and retinal pigment epithelium (RPE) express a relatively abundant mRNA that encodes an extraneous splice isoform of the RPE retinal G protein-coupled receptor (RGR) opsin. In this study, we investigate this exon-skipping RGR splice isoform (RGR-d) in separated neural retina and RPE cells of human donors of various ages.

Methods: We used mass spectrometry, sensitive western blot assay, immunohistochemical localization and real-time RT-PCR to analyze RGR-d.

Exon-skipping variant of RGR opsin in human retina and pigment epithelium.

An extraneous exon-skipping mRNA encodes an altered form of a light-absorbing opsin in human retina and pigment epithelium (RPE). The predicted protein variant differs from full-length RPE-retinal G protein-coupled receptor (RGR) by having an in-frame deletion of exon 6, which contains the entire sixth transmembrane domain. To verify that the exon 6-deleted RGR protein (RGR-d) exists in human retinas, we have produced RGR-d antibody probes.

Recovery of visual functions in a mouse model of Leber congenital amaurosis.

The visual process is initiated by the photoisomerization of 11-cis-retinal to all-trans-retinal. For sustained vision the 11-cis-chromophore must be regenerated from all-trans-retinal. This requires RPE65, a dominant retinal pigment epithelium protein.

Synthesis of the all-trans-retinal chromophore of retinal G protein-coupled receptor opsin in cultured pigment epithelial cells.

Light-dependent production of 11-cis-retinal by the retinal pigment epithelium (RPE) and normal regeneration of rhodopsin under photic conditions involve the RPE retinal G protein-coupled receptor (RGR) opsin. This microsomal opsin is bound to all-trans-retinal which, upon illumination, isomerizes stereospecifically to the 11-cis isomer. In this paper, we investigate the synthesis of the all-trans-retinal chromophore of RGR in cultured ARPE-hRGR and freshly isolated bovine RPE cells.