Increased serum proteins in non-exudative AMD retinas

Hannah Schultz, Ying Song, Bailey H. Baumann, Becky Kapphahn, Sandra Rocio Montezuma, Deborah A Ferrington, Joshua L. Dunaief

Research output: Contribution to journalArticle

Abstract

The blood retinal barrier (BRB) closely regulates the retinal microenvironment. Its compromise leads to the accumulation of retinal fluid containing potentially harmful plasma components. 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 subclinically compromised, allowing entry of retina-toxic plasma proteins. We test this hypothesis by measuring retinal levels of abundant plasma proteins that should not cross the intact BRB. Two cohorts of frozen, post mortem neurosensory retinas were studied by Western analysis. One cohort from Alabama had 4 normal controls and 4 eyes with various forms of AMD. Another cohort from Minnesota had 5 intermediate AMD eyes and 5 normals. Both cohorts were age/post mortem interval (PMI) matched. The non-exudative AMD retinas in the Alabama cohort had significantly higher levels of albumin and complement component 9 (C9) than normal controls. The positive control exudative AMD donor retina had higher levels of all but one serum protein. In both macular and peripheral neurosensory retina samples, intermediate AMD retinas in the Minnesota cohort had significantly higher levels of albumin, fibrinogen, IgG, and C9 than controls. Our results suggest that there may be moderate subclinical BRB leakage in non-exudative AMD. Potentially harmful plasma components including complement or iron could enter the neurosensory retina in AMD patients prior to advanced disease. Thus, therapies aiming to stabilize the BRB might have a role in the management of non-exudative AMD.

Original languageEnglish (US)
Article number107686
JournalExperimental Eye Research
Volume186
DOIs
StatePublished - Sep 1 2019

Fingerprint

Macular Degeneration
Retina
Blood-Retinal Barrier
Blood Proteins
Albumins
Complement C9
Poisons
Fibrinogen
Iron
Immunoglobulin G
Tissue Donors

Keywords

  • Age-related macular degeneration (AMD)
  • Albumin
  • Blood retinal barrier (BRB)
  • Complement factor 9 (C9)
  • Fibrinogen
  • IgG
  • Iron
  • Retina

Cite this

Increased serum proteins in non-exudative AMD retinas. / Schultz, Hannah; Song, Ying; Baumann, Bailey H.; Kapphahn, Becky; Montezuma, Sandra Rocio; Ferrington, Deborah A; Dunaief, Joshua L.

In: Experimental Eye Research, Vol. 186, 107686, 01.09.2019.

Research output: Contribution to journalArticle

@article{45bf342a900c4a0fa8bc4da12c3eab8e,
title = "Increased serum proteins in non-exudative AMD retinas",
abstract = "The blood retinal barrier (BRB) closely regulates the retinal microenvironment. Its compromise leads to the accumulation of retinal fluid containing potentially harmful plasma components. 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 subclinically compromised, allowing entry of retina-toxic plasma proteins. We test this hypothesis by measuring retinal levels of abundant plasma proteins that should not cross the intact BRB. Two cohorts of frozen, post mortem neurosensory retinas were studied by Western analysis. One cohort from Alabama had 4 normal controls and 4 eyes with various forms of AMD. Another cohort from Minnesota had 5 intermediate AMD eyes and 5 normals. Both cohorts were age/post mortem interval (PMI) matched. The non-exudative AMD retinas in the Alabama cohort had significantly higher levels of albumin and complement component 9 (C9) than normal controls. The positive control exudative AMD donor retina had higher levels of all but one serum protein. In both macular and peripheral neurosensory retina samples, intermediate AMD retinas in the Minnesota cohort had significantly higher levels of albumin, fibrinogen, IgG, and C9 than controls. Our results suggest that there may be moderate subclinical BRB leakage in non-exudative AMD. Potentially harmful plasma components including complement or iron could enter the neurosensory retina in AMD patients prior to advanced disease. Thus, therapies aiming to stabilize the BRB might have a role in the management of non-exudative AMD.",
keywords = "Age-related macular degeneration (AMD), Albumin, Blood retinal barrier (BRB), Complement factor 9 (C9), Fibrinogen, IgG, Iron, Retina",
author = "Hannah Schultz and Ying Song and Baumann, {Bailey H.} and Becky Kapphahn and Montezuma, {Sandra Rocio} and Ferrington, {Deborah A} and Dunaief, {Joshua L.}",
year = "2019",
month = "9",
day = "1",
doi = "10.1016/j.exer.2019.05.026",
language = "English (US)",
volume = "186",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Increased serum proteins in non-exudative AMD retinas

AU - Schultz, Hannah

AU - Song, Ying

AU - Baumann, Bailey H.

AU - Kapphahn, Becky

AU - Montezuma, Sandra Rocio

AU - Ferrington, Deborah A

AU - Dunaief, Joshua L.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - The blood retinal barrier (BRB) closely regulates the retinal microenvironment. Its compromise leads to the accumulation of retinal fluid containing potentially harmful plasma components. 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 subclinically compromised, allowing entry of retina-toxic plasma proteins. We test this hypothesis by measuring retinal levels of abundant plasma proteins that should not cross the intact BRB. Two cohorts of frozen, post mortem neurosensory retinas were studied by Western analysis. One cohort from Alabama had 4 normal controls and 4 eyes with various forms of AMD. Another cohort from Minnesota had 5 intermediate AMD eyes and 5 normals. Both cohorts were age/post mortem interval (PMI) matched. The non-exudative AMD retinas in the Alabama cohort had significantly higher levels of albumin and complement component 9 (C9) than normal controls. The positive control exudative AMD donor retina had higher levels of all but one serum protein. In both macular and peripheral neurosensory retina samples, intermediate AMD retinas in the Minnesota cohort had significantly higher levels of albumin, fibrinogen, IgG, and C9 than controls. Our results suggest that there may be moderate subclinical BRB leakage in non-exudative AMD. Potentially harmful plasma components including complement or iron could enter the neurosensory retina in AMD patients prior to advanced disease. Thus, therapies aiming to stabilize the BRB might have a role in the management of non-exudative AMD.

AB - The blood retinal barrier (BRB) closely regulates the retinal microenvironment. Its compromise leads to the accumulation of retinal fluid containing potentially harmful plasma components. 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 subclinically compromised, allowing entry of retina-toxic plasma proteins. We test this hypothesis by measuring retinal levels of abundant plasma proteins that should not cross the intact BRB. Two cohorts of frozen, post mortem neurosensory retinas were studied by Western analysis. One cohort from Alabama had 4 normal controls and 4 eyes with various forms of AMD. Another cohort from Minnesota had 5 intermediate AMD eyes and 5 normals. Both cohorts were age/post mortem interval (PMI) matched. The non-exudative AMD retinas in the Alabama cohort had significantly higher levels of albumin and complement component 9 (C9) than normal controls. The positive control exudative AMD donor retina had higher levels of all but one serum protein. In both macular and peripheral neurosensory retina samples, intermediate AMD retinas in the Minnesota cohort had significantly higher levels of albumin, fibrinogen, IgG, and C9 than controls. Our results suggest that there may be moderate subclinical BRB leakage in non-exudative AMD. Potentially harmful plasma components including complement or iron could enter the neurosensory retina in AMD patients prior to advanced disease. Thus, therapies aiming to stabilize the BRB might have a role in the management of non-exudative AMD.

KW - Age-related macular degeneration (AMD)

KW - Albumin

KW - Blood retinal barrier (BRB)

KW - Complement factor 9 (C9)

KW - Fibrinogen

KW - IgG

KW - Iron

KW - Retina

UR - http://www.scopus.com/inward/record.url?scp=85069557527&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069557527&partnerID=8YFLogxK

U2 - 10.1016/j.exer.2019.05.026

DO - 10.1016/j.exer.2019.05.026

M3 - Article

C2 - 31158383

AN - SCOPUS:85069557527

VL - 186

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

M1 - 107686

ER -