Abstract
Purpose :
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.
Methods :
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.
Results :
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.
Conclusions :
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.