Keratoconus is a progressive corneal thinning disease associated with significant tissue remodeling activities and activation of a variety of signaling networks. However, it is not understood how differential gene and protein expression direct function in keratoconus corneas to drive the underlying pathology, ectasia. Research in the field has focused on discovering differentially expressed genes and proteins and quantifying their levels and activities in keratoconus patient samples. In this study, both microarray analysis of total ribonucleic acid (RNA) and whole proteome analyses are carried out using corneal epithelium and tears from keratoconus patients and compared to healthy controls. A number of structural proteins, signaling molecules, cytokines, proteases, and enzymes have been found to be deregulated in keratoconus corneas. Together, the data provide clues to the complex process of corneal degradation which suggest novel ways to clinically diagnose and manage the disease. This review will focus on discussing these recent advances in the knowledge of keratoconus biology from a gene expression and function point-of-view.
Dry eye disease (DED) signs and symptoms are causally associated with increased ocular surface (OS) inflammation. Modulation of key regulators of aberrant OS inflammation is of interest for clinical management. We investigated the status and the potential to harness key endogenous protective factors, such as cystic fibrosis transmembrane conductance regulator (CFTR) and vitamin D receptor (VDR) in hyperosmotic stress-associated inflammation in patients with DED and in vitro. Conjunctival impression cytology samples from control subjects (n = 11) and patients with DED (n = 15) were used to determine the status of hyperosmotic stress (TonEBP/NFAT5), inflammation (IL-6, IL-8, IL-17A/F, TNFα, MMP9, and MCP1), VDR, and intracellular chloride ion (GLRX5) by quantitative polymerase chain reaction and/or immunofluorescence. Human corneal epithelial cells (HCECs) were used to study the effect of CFTR activator (genistein) and vitamin D (calcitriol) in hyperosmotic stress (HOs)-induced response in vitro. Western blotting was used to determine the expression of these proteins, along with p-p38. Significantly, higher expression of inflammatory factors, TonEBP, GLRX5, and reduced VDR were observed in patients with DED and in HOs-induced HCECs in vitro. Expression of TonEBP positively correlated with expression of inflammatory genes in DED. Increased TonEBP and GLRX5 provides confirmation of osmotic stress and chloride ion imbalance in OS epithelium in DED. These along with reduced VDR suggests dysregulated OS homeostasis in DED. Combination of genistein and calcitriol reduced HOs-induced TonEBP, inflammatory gene expression, and p-p38, and abated VDR degradation in HCECs. Henceforth, this combination should be further explored for its relevance in the management of DED. Dry eye disease (DED) is a chronic multifactorial condition of the ocular surface (OS), often associated with pain, discomfort and blurring of vision. 1 DED is characterized by tear-film instability, hyperosmolarity, OS inflammation and damage, and neurosensory abnormalities. 1 DED has evolved into one of the common public health concerns with a worldwide prevalence ranging up to 50%.
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