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Hyung Keun Lee, Yong woo Ji, Na Hyun Kim, Sun-Bi Um, Jong Suk Song, Wungrak Choi, Hyeon Chang Kim; Synergistic upregulation of neuropeptide Y and Y1 receptor found responsible for obesity-induced dry eye disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):398.
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the purpose of this study was to investigate the relationships between dry eye disease (DED) and obesity and to outline the mechanism by which obesity may lead to the development of DED. In a population-based cohort, we attempted to identify the relationships between DED and obesity. Also, using the db/db mouse model of obesity, pathologic changes in functional units of tear production were investigated in relation to changes in molecular markers of obesity.
Seven hundred twenty three cohort members, as well as male C57BL/KsJ-db/db mice for obesity (OB) and C57BL/KsJ-db/m mice for non-obese (NOB) controls were used for the present study. Patients were interviewed via a questionnaire to obtain information on socio-demographic characteristics and ocular surface disease index (OSDI) score, while blood sugar, and lipids were measured. For in vivo study, db/db and db/m male mice were used as a model of obesity and controls, respectively. A controlled environmental chamber was used to induce dry eye stress. Mice were scarified serially to obtain lacrimal glands (LGs) and corneas for measuring adipogenic factors and inflammatory cells with qPCR, ELISA, immunoblot, and flow cytometry.
With adjustment for age, sex, hypertension, diabetes, hypercholesterolemia, occupation, and lifestyle factors, body mass index (BMI) was associated with DED (odds ratio 3.34, p=0.0195). Interestingly, blue-collar workers and unemployed people reported significantly higher rates of DED than white-collar workers. Additionally, the association between high BMI and DED seemed stronger in men than in women (Odds ratio 11.59, p=0.0214 in men, 3.02, p=0.066 in women). Acinar cells in LGs from OB mice were replaced with fat cells. On ELISA, NPY was found to be significantly elevated in OB mice. Surprisingly, dry eye stress in OB mice synergistically enhanced NPY receptor Y1 expression by 23.1 fold, compared to controls. Under confocal microscopy, infiltration of NPY+ cells and pre-adipocytes increased with dry eye stress in OB mice.
Irrelative with hyperlipidemia, obesity is an independent risk factor for DED and contributes to the development and progression of DED, as fat cells infiltrate LGs. NPY and its receptor Y1 plays an essential role for obesity-induced DED and LG changes and may be targets for treating and preventing the DED progression.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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