Structural and biochemical analyses of choroidal thickness in human donor eyes

Elliott H Sohn; Aditi Khanna; Budd A Tucker; Michael D Abràmoff; Edwin M Stone; Robert F Mullins

doi:10.1167/iovs.13-13754

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Structural and biochemical analyses of choroidal thickness in human donor eyes

Journal article

Open access

Peer reviewed

Structural and biochemical analyses of choroidal thickness in human donor eyes

Elliott H Sohn, Aditi Khanna, Budd A Tucker, Michael D Abràmoff, Edwin M Stone and Robert F Mullins

Investigative ophthalmology & visual science, Vol.55(3), pp.1352-1360

03/06/2014

DOI: 10.1167/iovs.13-13754

PMCID: PMC3945900

PMID: 24519422

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Abstract

The choroid plays a vital role in the health of the outer retina. While measurements of choroid using optical coherence tomography show altered thickness in aging and macular disease, detailed histopathologic and proteomic analyses are lacking. In this study we sought to evaluate biochemical differences in human donor eyes between very thin and thick choroids. One hundred forty-one eyes from 104 donors (mean age ± standard deviation, 81.5 ± 12.2) were studied. Macular sections were collected, and the distance between Bruch's membrane and the inner surface of the sclera was measured in control, early/dry age-related macular degeneration (AMD), neovascular AMD, and geographic atrophy eyes. Proteins from the RPE-choroid of eyes with thick and thin choroids were analyzed using two-dimensional electrophoresis and/or mass spectrometry. Two proteins with altered abundance were confirmed using Western blot analysis. Donor eyes showed a normal distribution of thicknesses. Eyes with geographic atrophy had significantly thinner choroids than age-matched controls or early AMD eyes. Proteomic analysis showed higher levels of the serine protease SERPINA3 in thick choroids and increased levels of tissue inhibitor of metalloproteinases-3 (TIMP3) in thin choroids. Consistent with clinical imaging observations, geographic atrophy was associated with choroidal thinning. Biochemical data suggest an alteration in the balance between proteases and protease inhibitors in eyes that lie at the extremes of choroidal thickness. An improved understanding of the basic mechanisms associated with choroidal thinning may guide the development of new therapies for AMD.

Mass Spectrometry

Biomarkers - metabolism

Choroid - metabolism

Humans

Middle Aged

Electrophoresis, Gel, Two-Dimensional

Tomography, Optical Coherence - methods

Macular Degeneration - metabolism

Eye Proteins - metabolism

Aged, 80 and over

Aged

Tissue Donors

Choroid - pathology

Macular Degeneration - pathology

Details

Title: Subtitle: Structural and biochemical analyses of choroidal thickness in human donor eyes
Creators: Elliott H Sohn - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa
Aditi Khanna
Budd A Tucker
Michael D Abràmoff
Edwin M Stone
Robert F Mullins
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.55(3), pp.1352-1360
DOI: 10.1167/iovs.13-13754
PMID: 24519422
PMCID: PMC3945900
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: R01 EY016822 / NEI NIH HHS DP2 OD007483 / NIH HHS 1-DP2-OD007483-01 / NIH HHS Howard Hughes Medical Institute EY017451 / NEI NIH HHS R01 EY017451 / NEI NIH HHS EY016822 / NEI NIH HHS
Language: English
Date published: 03/06/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983806387402771

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