Abstract
Purpose :
Dry eye disease is a multifactorial disease that is characterized by tear film instability with increased osmolarity of the tear film, which damages the ocular surface and results in ocular surface inflammation. In this study, we investigated the treatment effects of collagen type II 1α based novel peptides GQDGLAGPK in a dry eye mouse model.
Methods :
An experimental dry eye model was induced in NOD●B10H2b mice through desiccation stress for 10 days. The mice were randomly divided into 4 groups according to the treatment regimen: the DS group (n=9), normal saline group (n=10, 5 μL of normal saline), GQDGLAGPK group (n=10, 5 μL of 10 mg/mL GQDGLAGPK) and commercial collagen type II group (n=10, 5 μL of 10 mg/mL collagen type II). All treatments instilled 5 times / day for 10 days. Tear volumes and corneal irregularity scores were measure at 3, 5, 7 and 10 days after treatment. At the end of the experiment, hematoxylin and eosin, periodic acid schiff staining and immunohistochemistry were performed on cornea, conjunctiva and lacrimal gland respectively.
Results :
The desiccation stress significantly decreased tear production (DS group, 0.04 ± 0.02 μL, p<0.05) compared baseline (0.22±0.03 μL). Moreover, the DS group had gradually increased detachment of corneal epithelial cells and overexpression of pro-inflammatory markers in lacrimal gland. The DS group had also decreased conjunctival goblet cells. However, the GQDGLAGPK group had significantly increased tear volumes (0.21±0.02 μl, p<0.05) and decreased corneal irregularity scores (1.33±0.82, p<0.05) compared with normal saline group and commercial collagen type II group. As results of histological examination, the number of detached corneal epithelial cells was significantly decreased by 63% and the density of conjunctival goblet cells was increased by 220% in GQDGLAGPK group compared to DS group. In additions, the GQDGLAGPK markedly suppressed expression of inflammatory-related factors including cytokines, adhesion molecules and MMPs in the lacrimal gland.
Conclusions :
In this study, we found that collagen type II α1 based peptide can help to improve ocular surface disorders of dry eye though increasing the tear volume, goblet cell density and corneal epithelium stabilization. Furthermore, GQDGLAGPK has the potential for use in eye drops as a treatment for dry eye disease with anti-inflammatory effects on the lacrimal functional unit.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.