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Mei Chen, Sofia Pavlou, Josy Augustine, Heping Xu; SIGIRR deficiency accelerates diabetes-induced retinal neurodegeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2656. doi: https://doi.org/.
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Inflammation is believed to play a critical role in the initiation and progression of diabetic retinopathy. Single Ig IL-1-related receptor (SIGIRR) is a negative regulator of the TLR/IL-1R signalling pathway. We have found that diabetes down-regulates SIGIRR expression. In this study, we examined diabetes-induced retinal neurodegeneration in SIGIRR deficient mice.
Diabetes was induced in C57BL/6J (WT) and SIGIRR-/- mice by intreperitoneal injection of Streptozocin (STZ). Retinal electroretinography (ERG) and Optical Coherence Tomography (OCT) were performed on 6-month diabetic mice. Retinal neurons were examined by confocal microscopy following immunostaining with cone arrestin, PKCα, synaptophysin and Brn3a. The expression of proinflammatory cytokines in the retina and bone marrow-derived macrophages were examined using qRT-PCR.
The SIGIRR-/- and WT mice developed similar levels of diabetes after STZ injection. The amplitudes of a- and b-wave were reduced in diabetic mice, which is correlated with the reduction in the number of photoreceptor and ganglion cells. The a- and b-wave amplitudes and numbers of photoreceptor and ganglion cells were significantly lower in SIGIRR-/- diabetic mice compared with their WT counterparts. The expression of CCL2, IL1b and IL18 genes was significantly higher in SIGIRR-/- diabetic retina than that in WT diabetic retina. Macrophages from SIGIRR-/- mice express significantly higher levels of iNOS, IL-1β, TNFα, IL-6 and CCL2 compared to those from WT mice, particularly under high-glucose conditions.
SIGIRR deficiency leads to uncontrolled inflammation and more severe retinal neurodegeneration under diabetes conditions.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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