title: Accumulation of extracellular RGR-d in Bruch's membrane and close association with drusen at intercapillary regions.
abstract: 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. RGR-d was analyzed in drusen and Bruch's membrane by immunohistochemical localization. Extracellular RGR-d is present in most drusen, including hard, soft, confluent and early-stage. Initial drusen formation is known to be preferentially associated with the intercapillary regions of Bruch's membrane. We corroborated this significant association of drusen, including early-stage drusen, with the intercapillary regions. The distribution of extracellular RGR-d in Bruch's membrane differs in old and young donors. In older persons, nodes of concentrated RGR-d accumulate at intercapillary loci, predominantly at the lateral edges of the capillaries of the choriocapillaris. RGR-d loci at the lateral capillary wall appear numerous in old, but not young, donors. Intensely immunostained RGR-d loci can be found at the base of early-stage drusen mounds in the older donors and may precede the formation of these drusen.
authors.affiliation: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Harold
authors.initials: H
authors.lastname: Kochounian
authors.forename: Lincoln V
authors.initials: LV
authors.lastname: Johnson
authors.forename: Henry K W
authors.initials: HK
authors.lastname: Fong
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D016570:Bruch Membrane / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015593:Retinal Drusen / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D055815:Young Adult
chemical_list: D005136:Eye Proteins; C089754:G protein-coupled receptor RGR; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled