July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Blood retinal barrier disruption in non-exudative AMD
Author Affiliations & Notes
  • Hannah Schultz
    F.M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, United States
  • Ying Song
    F.M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, United States
  • Rebecca J Kapphahn
    Ophthalmology & Visual Neuroscience, University of Minnesota, Minnesota, United States
  • Sandra Rocio Montezuma
    Ophthalmology & Visual Neuroscience, University of Minnesota, Minnesota, United States
  • Deb A Ferrington
    Ophthalmology & Visual Neuroscience, University of Minnesota, Minnesota, United States
  • Joshua L Dunaief
    F.M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Hannah Schultz, None; Ying Song, None; Rebecca Kapphahn, None; Sandra Montezuma, None; Deb Ferrington, None; Joshua Dunaief, None
  • Footnotes
    Support  NIH/NEI EY015240, Research to Prevent Blindness Medical Student Research Award and unrestricted funds, the Jeffrey W. Berger, MD, PhD Foundation, the F.M. Kirby Foundation, a gift in memory of Lee F. Mauger, MD, and the Paul and Evanina Bell Mackall Foundation Trust
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4890. doi:
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    • Get Citation

      Hannah Schultz, Ying Song, Rebecca J Kapphahn, Sandra Rocio Montezuma, Deb A Ferrington, Joshua L Dunaief; Blood retinal barrier disruption in non-exudative AMD. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4890.

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

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Abstract

Purpose : The blood retinal barrier (BRB) closely regulates the retinal microenvironment. Its compromise leads to the accumulation of retinal fluid containing serum components that could harm the retina. While eyes with non-exudative age-related macular degeneration (AMD) were previously felt to have an intact BRB, we propose that the BRB in non-exudative AMD eyes may be moderately compromised. We test this hypothesis by quantifying and localizing abundant serum proteins that should not cross the intact BRB.

Methods : Postmortem retinas were obtained from human AMD (n=4) and non-AMD (n=4) donors. Accumulation of albumin, IgG, complement factor 9 (C9) and the membrane attack complex (MAC) within neurosensory retinas was assessed by semiquantitative Western analysis. Student’s two-tailed unpaired t-test was used for statistical analysis. Additionally, immunohistochemistry (IHC) was used to localize extravasation and accumulation of these serum proteins in neurosensory retinas of post mortem human AMD eyes (n=2) and non-AMD eyes (n=2) from a different cohort of donors.

Results : Semiquantitative Western analysis demonstrated a significant increase in levels of albumin, C9, and MAC within neurosensory retinas of AMD donors as compared to donors without AMD. In addition, there was a non-significant 1.75 fold increase in IgG heavy chain levels, and a non-significant 2.6 fold increase in IgG light chain levels. Serum protein levels were highest in the exudative AMD donor which is expected and validates our technique. This donor was excluded from statistical analysis because we wished to determine whether serum proteins leak into the retina in non-exduative eyes specifically. IHC showed more intense IgG, Albumin, and MAC label in non-exudative AMD retinas compared to normals, with particular localization to the apical retinal pigment epithelium (RPE) and photoreceptor layer. Labeling of C9 was not observed in either AMD or normal retinas.

Conclusions : Our results suggest that there may be moderate BRB leakage in non-exudative AMD, with accumulation of serum proteins preferentially in the apical RPE and photoreceptor layer. IHC with the C9 antibody may have been negative because this antibody may be unable to detect C9 when in the MAC complex or when it is non-denatured. Overall, these findings suggest that therapies aiming to stabilize the BRB, potentially including anti-VEGF agents, might have a role in the management of non-exudative AMD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

 

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