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Robert Mullins, Aditi Khanna, Kai Wang, Megan Riker, Edwin Stone, Elliott Sohn; Human choroidal thickness: Relationship to protease inhibitors. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3196.
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Altered choroidal thickness has been described in association with a number of disease conditions, including glaucoma, age-related macular degeneration, central serous chorioretinopathy, and polypoidal vasculopathy. In addition, a clinical entity “age-related choroidal atrophy” has recently been described. We performed a pilot study to understand the structural and biochemical factors that may contribute to choroidal thickness.
From a collection of archived human donor eyes at the University of Iowa Institute for Vision Research, 124 eyes from 87 donors were evaluated for choroidal thickness on hematoxylin-eosin stained macular sections by measuring the distance between Bruch’s membrane and the sclera. Selected examples of unfixed RPE-choroid tissue from among the thickest and thinnest samples were pooled and used for 2D gel electrophoresis and/or shotgun proteomics. Validation of enriched proteins was performed by Western blot and/or immunofluorescence.
Human eyes in our collection showed a normal distribution of choroidal thickness. The average thickness was 155µm with a standard deviation of 69µm. These values are lower than normally seen in perfused, living eyes by OCT. For samples for which other morphometric data were available, no association was noted between choroidal thickness and choriocapillaris density. Eyes with age-related macular degeneration had slightly thinner choroids than controls (~15%) but this did not reach statistical significance. When comparing 2D gels of thick and thin choroid pools, a number of differences were apparent. A subset of these spots were successfully identified, and included alpha-1-antitrypsin and alpha-1-antichymotrypsin. Shotgun proteomics revealed TIMP3 to be the most pronounced difference between thin and thick choroids (base 2 log ratio = 6.5). Surprisingly, this protein was much more abundant in thin choroids than thick. This difference was confirmed on 5 thin choroids and 5 thick choroids by Western blot.
Although choroidal thickness is related to pathologic conditions, the genetic and biochemical factors responsible for this phenotype have not been described. This study suggests that alterations in the protease-protease inhibitor axis contribute to extremes of choroidal thickness in humans.
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