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Laura Soriano-Romani, Orla Galvin, Rob Jones, Sharon Cheetham, Yolanda Diebold; Characterization of inflammatory changes in lacrimal glands in a mouse model of type 2 diabetes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3947.
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© ARVO (1962-2015); The Authors (2016-present)
Around 70 % of diabetic patients suffer from ocular surface complications. Although the aetiology underlying the development of these complications remains unclear, rodent diabetic models maybe a helpful tool to study the physiopathology of the disease. In this study we have characterized the inflammatory changes in lacrimal glands in a mouse model of type 2 diabetes induced by the combination of a high-fat diet (HFD) and low-dose streptozotocin (STZ).
Male C57BL/6J mice were placed on a HFD (60 %, D12492, Research diets) for 4 weeks prior to administration of STZ (50 mg/kg ip) or vehicle (ip) for 5 days. After 15 weeks, terminal blood was taken and lacrimal glands removed and weighed. Plasma glucose and blood HbA1c were quantified to assess diabetic status. Lacrimal glands were processed, embedded and sectioned (5 μm). Advanced glycation end (AGE) products and interleukin(IL)-1β were evaluated by immunofluorescence. Cell death was analysed by TUNEL staining. Immunostaining intensities were assessed using ImageJ software. Hematoxylin and eosin stained lacrimal gland tissue sections allowed for the scoring and analysis of inflammatory infiltrates.
Glucose (34.45 ± 0.63 vs 15.74 ± 0.39; mean ± SEM; mM) and HbA1c (9.74 ± 0.10 vs 5.51 ± 0.07; mean ± SEM; %) levels were significantly higher (p<0.001; n=12-15) in HFD/STZ than in HFD mice. Lacrimal gland weights (9.46 ± 0.55 vs 14.17 ± 0.62; mean ± SEM; mg) were significantly lower (p<0.001; n=12-15) in HFD/STZ than in HFD mice, although the ratio between lacrimal gland weight (mg)/body weight (g) was not significantly altered. Preliminary data using fluorescent intensities revealed increased levels of IL-1β (p<0.05; n=6) and TUNEL (p=0.08; n=6) in HFD/STZ lacrimal glands when compared to HFD lacrimal glands. In contrast, no differences in AGE immunostaining or scored number of infiltrates were observed (n=9-10).
Lacrimal glands from diabetic HFD/STZ mice exhibit increased inflammatory markers compared to those from control mice on a HFD. These data suggest that investigation of inflammation-based changes in conjunctival and corneal tissues is warranted. Furthermore, this model of type 2 diabetes may address the need for better models to enhance the knowledge of the diabetic ocular surface disorders and a novel research tool to advance therapeutics in this field.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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