Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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 large and early-stage drusen mounds in the older donors and may precede the formation of these drusen.
Conclusions: :
Observable differences in the localized concentration of extracellular RGR-d exist between normal young individuals and older donors with age-related changes in Bruch's membrane. In older donors, the accumulation of extracellular RGR-d becomes concentrated at intercapillary regions.
Keywords: Bruch's membrane • drusen • proteins encoded by disease genes