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Rachida Bouhenni, Deepak Edward, Sandeep Grover, Kakarla Chalam, Abby Sewell, Khaled Abu-Amero; The Aqueous Humor Proteome in Patients with Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1157. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To identify differences in the protein composition of the aqueous humor (AH) of patients with diabetic retinopathy (DR) compared to patients without history of diabetes undergoing cataract surgery (control).
AH samples (n=6 for control and n=7 for DR) were analyzed by Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) and relative protein abundances were determined by spectral counting. G test followed by post hoc Holm Sidak was used for statistical analyses to determine significance in the differential expression of proteins between DR and control groups. Proteins were classified into functional groups using Scaffold 3.0.
Using stringent filtering criteria, seven proteins were significantly altered in the DR AH (p<0.05). SERPINF1 (PEDF), complement factor B (CFB), lumican and complement C9 (C9) were detected at higher levels (1.5,1.6, 2 and 3 fold respectively), whereas serotransferrin (TF), SERPING1 and prostaglandin-H2 D-isomerase (PTGDS) were detected at lower levels (0.77, 0.72 and 0.55 fold respectively) in DR AH compared to control. The altered proteins are involved in angiogenesis, inflammation, lipid metabolism and cell proliferation. Three of the proteins: TF, CFB and PTGDS are associated with serine and serine-inhibitor peptidase activity. Serine-inhibitor peptidases display anti-inflammatory and angiogenic activities, both of which have been previously implicated in DR. Lumican is expressed in fibrotic lens epithelial cells and deposited in glomeruli in advanced diabetic nephropathy.
Analysis of AH from DR eyes using LC-MS/MS revealed significant differences in protein expression compared to control. Lumican and serine-inhibitor peptidases dominated the differential protein profile of DR (4/7; 57.2%). The source of elevated lumican, typically expressed in the cornea, could be the neuroepithelial lining of the uveal tract or lens epithelial cells of DR eyes, whereas the serine-inhibitor peptidases could be derived from multiple sources.SERPINF1 elevation in AH may reflect a protective anti angiogenic effect of the molecule in the anterior segment in DR eyes.
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