July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
SIGIRR deficiency accelerates diabetes-induced retinal neurodegeneration
Author Affiliations & Notes
  • Mei Chen
    Centre for Experimental Medicine, Queens University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Sofia Pavlou
    Centre for Experimental Medicine, Queens University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Josy Augustine
    Centre for Experimental Medicine, Queens University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Heping Xu
    Centre for Experimental Medicine, Queens University Belfast, Belfast, NORTHERN IRELAND, United Kingdom
  • Footnotes
    Commercial Relationships   Mei Chen, None; Sofia Pavlou, None; Josy Augustine, None; Heping Xu, None
  • Footnotes
    Support  Fight for Sight UK (REF 1574/1575)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2656. doi:
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    • Get Citation

      Mei Chen, Sofia Pavlou, Josy Augustine, Heping Xu; SIGIRR deficiency accelerates diabetes-induced retinal neurodegeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2656.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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