title: Structural and biochemical analyses of choroidal thickness in human donor eyes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, Iowa.
authors: Elliott H
authors: EH
authors: Sohn
authors: Aditi
authors: A
authors: Khanna
authors: Budd A
authors: BA
authors: Tucker
authors: Michael D
authors: MD
authors: Abràmoff
authors: Edwin M
authors: EM
authors: Stone
authors: Robert F
authors: RF
authors: Mullins
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002829:Choroid / Q000378:metabolism / Q000473:pathology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005136:Eye Proteins / Q000378:metabolism*; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology*; D013058:Mass Spectrometry; D008875:Middle Aged; D014019:Tissue Donors; D041623:Tomography, Optical Coherence / Q000379:methods*
chemical_list: D015415:Biomarkers; D005136:Eye Proteins
keywords: age-related macular degeneration; choroid; protease