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Kevin Harkin, Mei Chen, Heping Xu, Sofia Pavlou; The inflammasome pathway is activated in the retina of type 2 but not type 1 diabetic mice. Invest. Ophthalmol. Vis. Sci. 2019;60(9):768. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) can occur in both type 1 and type 2 diabetes. Inflammation is known to play an important role in the pathogenesis of DR although the underlying mechanism is not fully understood. The inflammasome pathway critically controls the production and maturation of pro-inflammatory cytokines, such as Interleukin 1 beta (Il1b) and Interleukin 18 (Il18). This study aimed to understand if the inflammasome pathway is active in the retina of type 1 and type 2 diabetic mice.
Two murine models of type 1 diabetes (Ins2Akita mice and Streptozotocin-induced diabetes in C57BL/6J mice) and one model of type 2 diabetes (BKsCgm+/+lepr) were used. Eyes were collected from mice with 6-month diabetes and gender-age-matched healthy controls. The mRNA and protein expression of Nlrp3, Aim2, Caspase1, Caspase4, Il18, and Il1b was examined by qRT-PCR, Western blot, and immunohistochemistry.
The three types of diabetic mice had similarly high levels of blood glucose compared to non-diabetic controls. The expression levels of Nlrp3, Aim2, Caspase 4, Caspase 1 and Il1b in the retinas of BKsCgm+/+lepr mice were significantly increased compared to those from aged-matched control mice (BKsCgm+/-lepr). Interestingly, the retinal expression level of Nlrp3, Aim2, Caspase 4 of Ins2Akita mice and STZ-induced type 1 diabetic mice was comparable to that from age-matched non-diabetic control C57BL/6J mice.
The inflammasome pathway is activated in the retina of type 2, but not type 1 diabetic mice. Our results suggest that different inflammatory pathways may be involved in the development of DR in type 1 and type 2 diabetes.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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