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

Exp Eye Res. 2009 Jun;88(6):1129-36. doi: 10.1016/j.exer.2009.01.019. Epub 2009 Feb 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Aged, 80 and over
  • Aging / metabolism
  • Bruch Membrane / metabolism*
  • Extracellular Space / metabolism
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Humans
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Retinal Drusen / metabolism*
  • Retinal Pigment Epithelium / metabolism
  • Young Adult

Substances

  • Eye Proteins
  • G protein-coupled receptor RGR
  • Protein Isoforms
  • Receptors, G-Protein-Coupled