Year: 2020 | Month: December | Volume 10 | Issue 6
Down-Regulation of Rho GTPase-Activating Protein 7 (DLC1) in Tear Film and Modulation of Rho GTPase Dynamics by Rosuvastatin in Dogs Suffering from Keratoconjunctivitis Sicca
Rho GTPases activity in tear fluid as well as ocular surface epithelium (OSEC) during progression of Keratoconjunctivitis sicca (KCS) and their modulation with Rosuvastatin in dogs was studied. Based on Schirmer’s tear test, KCS cases were staged as early (n= 21) and late KCS (N=14). Tear and ocular surface epithelial cell samples were collected from all cases for protein and gene expression studies. Rho GTPase activity in different stages of KCS was evaluated by tear fluid 1D-SDS-PAGE, MALDI-TOF/MS, western blotting and corneal tissue immuno-histochemistry (IHC). Protein expression studies showed increased expression of Rho GTPases in early and late KCS. Effect of Rosuvastatin on progression of KCS was evaluated on 12 client owned dogs divided into two groups A (control group) and B (treatment group) having six dogs in each. Group A dogs were treated with topical eye drops alone whereas, group B animals were treated with topical eye drops and Rosuvastatin orally @ 0.2 mg/kg B.W. 14 days. Tear proteomic study revealed significant down-regulation of Rho GTPase-activating protein 7 (DLC1) and up-regulation Rho modulators and Ras-related Rab proteins in KCS cases. Group B dogs showed better response in terms of corneal clarity both clinically and photographically compared to group A. Expression of Rho GTPase proteins was increased in group B compared A post treatment. On Real-Time PCR assay, mRNA expression of RhoA and GDI2 was contained post Rosuvastatin treatment in OSCEs. Rosuvastatin treatment reduced the gene expression of Rho GTPases and blocked the progression of KCS in dogs.
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