Year: 2021 | Month: February | Volume 11 | Issue 1
Wnt Target Proteins Up-Regulated in Tear Film of Corneal Ulcer Mediates YAP1 Activation and Corneal Pathology in Dogs Suffering from Keratoconjunctivitis Sicca
Sasikala R.
Aswathy Gopinathan
Kiranjeet Singh
Swapana CR
Akshay Kumar
Sowbharenya Chelladuraai
Monalisa Sahoo
Ravi Kant Agrawal
DOI:10.30954/2277-940X.01.2021.20
Abstract:
The study was performed to identify Wnt and YAP1 target proteins and regulators in the tear fluid and the role of Timolol (0.5% w/v) in corneal wound healing by mediating YAP1 activation in dogs suffering from corneal ulcer due to Keratoconjunctivitis sicca (KCS). Complete clinical examination, the staging of KCS cases, and tear fluid collection were done. Protein identification from tryptic peptides of tear fluid of KCS cases was done through Matrix-assisted laser desorption/ ionization-time of flight mass spectrometry (MALDI-TOF/ MS). Dynamics of YAP1 and its downstream targets CTGF and E-Cadherin in Tear fluid through immuno-blotting and in-situ detection through Immuno-histochemistry (IHC) was done. The role of Timolol (0.5% w/v) in the corneal healing through activation of YAP and CTGF was studied. Wnt target proteins like Frizzled-6 (FZD6), Catenin beta1(CTNNB1), G1/S-specific cyclin-D1(CCND1), Vascular cell adhesion protein-1 (VCAM-1), and Matrix metalloproteinase-9 (MMP-9) were found significantly up-regulated (p<0.05) in corneal ulcer (KCS). YAP1 regulators Tyrosine-protein kinase Yes (YES1) was found significantly up-regulated (p<0.05) whereas Leukemia inhibitory factor receptor (LIFR), Angiopoietin-1 (Ang-1) and Rho GTPase-activating protein 7 (DLC1) (p<0.001), Tight junction protein ZO-3 (TJP3), and Cadherin-1 (CDH1) (p<0.05) were significantly down-regulated in corneal ulcer compared to normal tear. Increased expression of YAP1 and CTGF was observed in the tear film and corneal tissues of corneal ulcer cases. Up-regulation of the Wnt target proteins and YAP1 activation occurred in corneal ulcer due to KCS and orchestrated characteristic corneal pathology. Timolol enhanced cell proliferation and thus was helpful in corneal healing but augmented KCS pathology in corneal tissue.
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