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Arkasubhra Ghosh, Rohit Shetty, Lei Zhou, Sharon D'Souza, Roger Beuerman; Identification of biomarkers for disease progession of Keratoconus. Invest. Ophthalmol. Vis. Sci. 2013;54(15):928.
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Keratoconus (KC) is a corneal disease, which is characterized by corneal thinning leading to loss of visual acuity through ectasia and irregular astigmatism. Clinically, the symptoms of KC can be highly variable and in part, depend on the stage of the progression of the disorder as well as associated eye-rubbing, itching, etc. There is currently no effective management for KC, nor any adequate biomarkers to predict the outcome of clinical severity of the disease. Furthermore, there is considerable confusion in the field regarding the pathophysiology of the disease and key involvement of inflammation. To that end, this study was designed to address these questions.
We correlated the clinical features associated with KC in a cohort of 54 patients with tear proteomic profiles. This non-interventional study was approved by the Narayana Nethralaya IRB. Clinical grades and associated symptoms were graded as per the Amsler-Krumeich classification (Grade I: 32 patients, Grade II: 14 patients, Grade III: 8 patients). Quantitative Proteomic analysis was carried out using iTRAQ with nanoLC-MS/MS on 25μg total tear protein from each patient and pooled healthy control subjects (n = 12) for comparison.
We observed that eye-rubbing correlated with increasing clinical grades and morbidity of KC. In total, over 1000 tear proteins (< 1% false discovery rate) were identified from the whole study. Quantitative proteomic results from a group of up-regulated and down-regulated proteins (ratio for KC/control > 1.5, or < 0.67) revealed a positive correlation between several tear proteins (LCN1, PLA2G2A, SCGB2A1, MSLN and CRYAB) and KC clinical grades (Grade I, II and III). A negative correlation between a group of tear proteins (ALB, IGHG2 & G3, A2M, complement factors C3, C4A, C6 & H, ORM1, KNG1, PRDX1, SERPIN-F1, GSN) and KC clinical grades was also observed.
These proteins could be used alone or in combination as biomarkers for predicting the progression or severity of keratoconus. These proteins also shed light on the underlying deregulation of important inflammatory and immunomodulatory pathways that may be key drivers of KC pathophysiology.
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