April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Accumulation of Extracellular RGR-d in Bruch's Membrane and Close Association With Drusen at Intercapillary Regions
Author Affiliations & Notes
  • H. Kochounian
    Molecular Microbiology and Immunology, University of Southern California, Los Angeles, California
  • L. V. Johnson
    Center for the Study of Macular Degeneration, University of California Santa Barbara, Santa Barbara, California
  • H. K. W. Fong
    Doheny Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California
  • Footnotes
    Commercial Relationships  H. Kochounian, None; L.V. Johnson, None; H.K.W. Fong, None, P.
  • Footnotes
    Support  NIH Grants EY03040 and EY08364 (HKWF), EY11527 and EY17404 (LVJ), Research to Prevent Blindness, and the Gordon and Evelyn Leslie Macular Degeneration Fund
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4176. doi:
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      H. Kochounian, L. V. Johnson, H. K. W. Fong; Accumulation of Extracellular RGR-d in Bruch's Membrane and Close Association With Drusen at Intercapillary Regions. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4176.

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      © ARVO (1962-2015); The Authors (2016-present)

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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 

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