Anti-inflammatory effect of hydroxyproline-GQDGLAGPK in desiccation stress-induced experimental dry eye mouse

Abstract

The purpose of this study has been the investigation of the effect of novel peptide hydroxyproline-GQDGLAGPK (Hyp-GQDGLAGPK) in desiccation stress-induced dry eye mouse model and compared medicines for dry eye disease including cyclosporine, diquafosol and sodium hyaluronate. Seventy eight NOD.B10.H2 b mice were injected with scopolamine and exposed to an air draft for 10 days, and then the mice were treated with normal saline (n = 13), 1% Hyp-GQDGLAGPK (n = 13), 0.05% cyclosporine (n = 13), 3% diquafosol (n = 13), and 0.1% hyaluronate (n = 13) for 10 days. Thirteen mice were used for histopathologic analysis at DS 10d. The desiccation stress significantly decreased tear production, but the topical treatment of Hyp-GQDGLAGPK recovered to the baseline levels, which was similar to cyclosporine and diquafosol. In addition, Hyp-GQDGLAGPK improved facilitating epithelium stabilization including the corneal irregularity score, fluorescein score and detachment of the corneal epithelium. These improvements in stabilization of the corneal epithelium was superior to that in the cyclosporine and sodium hyaluronate groups. Furthermore, desiccation stress markedly induced expression of autoimmune inflammation-related factors in the lacrimal glands, but it was significantly suppressed by Hyp-GQDGLAGPK treatment. Overall, we found that novel peptide Hyp-GQDGLAGPK has multi-functional effects such as stabilizing the tear film and inhibiting inflammation.

A New Ophthalmic Pharmaceutical Formulation, Topical Sulglycotide, Enhances the Ocular Mucin Secretion in Desiccation Stress-Mediated Dry Eye Disease

“…Several studies suggested that the detachment of corneal epithelium is one of the ways of assessing damage of the ocular surface in DE. 25,26,30,31 In the present study, 4% SOS gradually suppressed the detachment of epithelium by desiccation stress, and it was similar to results from the control group and the DQS group (Fig. 4).…”

“…45 Our previous studies suggested that desiccation stress upregulated the expression of inflammatory markers including TNFa, ICAM-1, VCAM-1, MMP-2, and MMP-9 in the lacrimal gland. 25,26,31 Likewise, the present study shows the desiccation stress-mediated overexpression of inflammatory factors such as cytokine, adhesion molecules, and MMPs, whereas these factors were markedly decreased by topical SOS treatment in a dose-dependent manner (Fig. 8).…”

“…Forty-six mice were subjected to desiccating stress for 10 days that exposed them to an air draft with a fan, as previously reported. 25,26 At the same time, 0.5 mg/ 200 lL of the muscarinic receptor blocker, scopolamine hydrobromide (Sigma-Aldrich, St. Louis, MO, USA), was injected subcutaneously four times a day. At 10 days after desiccating stress (DS 10d), we measured the tear amount and corneal irregularity score.…”

“…The tear volume was evaluated as previously described. 26,27 Briefly, the tear amount was evaluated with phenol redimpregnated cotton threads (Zone-Quick; Oasis, Glendora, CA, USA) for 20 seconds. The tear volume was measured at 2 hours after the last scopolamine injection and at 1 hour after the last treatment in both eyes and calculated with a standard curve of response to a stock basic solution (1.5 L 0.9% saline and 5 mL 5 N NaOH).…”

“…For the evaluation of the detaching epithelium, the sections were stained with hematoxylin and eosin (H&E). 26 For evaluating the density of conjunctival goblet cells, the conjunctival sections were stained with periodic acid Schiff (PAS), and the test was performed using a commercial kit (Merck, Darmstadt, Germany) according to the manufacturer's instructions. The sections were photographed with a virtual microscope (Nano-Zoomer 2.0 RS; Hamamatsu Photonics, Shizuoka Prefecture, Japan).…”