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. In Western blot assays, the RGR-d protein was detected in retinas of a large proportion (∼53%) of individual donors, including patients with age-related macular degeneration (AMD). The relative abundance of RGR-d varied significantly between individuals. The altered protein is expressed in RPE cells and has a more basal subcellular localization that is remarkably different from that of normal RGR opsin. The presence of this exon-skipping variant of RGR in humans may contribute to the progressive derangement of the RPE.