CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes

Eleni Beli, James M Dominguez, Ping Hu, Jeffrey S Thinschmidt, Sergio Caballero, Sergio Li Calzi, Defang Luo, Sumathi Shanmugam, Tatiana E Salazar, Yaqian Duan, Michael E Boulton, Susanna Mohr, Steven F Abcouwer, Daniel R Saban, Jeffrey K Harrison, Maria B Grant

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

In this study, the role of CX3CR1 in the progression of diabetic retinopathy (DR) was investigated. The retinas of wild-type (WT), CX3CR1 null (CX3CR1gfp/gfp, KO), and heterozygous (CX3CR1+/gfp, Het) mice were compared in the presence and absence of streptozotocin (STZ)-induced diabetes. CX3CR1 deficiency in STZ-KO increased vascular pathology at 4 months of diabetes, as a significant increase in acellular capillaries was observed only in the STZ-KO group. CX3CR1 deficiency and diabetes had similar effects on retinal neurodegeneration measured by an increase in DNA fragmentation. Retinal vascular pathology in STZ-KO mice was associated with increased numbers of monocyte-derived macrophages in the retina. Furthermore, compared to STZ-WT, STZ-KO mice exhibited increased numbers of inflammatory monocytes in the bone marrow and impaired homing of monocytes to the spleen. The induction of retinal IL-10 expression by diabetes was significantly less in KO mice, and when bone marrow-derived macrophages from KO mice were maintained in high glucose, they expressed significantly less IL-10 and more TNF-α in response to LPS stimulation. These findings support that CX3CR1 deficiency accelerates the development of vascular pathology in DR through increased recruitment of proinflammatory myeloid cells that demonstrate reduced expression of anti-inflammatory IL-10.
Original languageEnglish
Pages (from-to)1255–1265
Number of pages11
JournalJournal of Molecular Medicine
Volume94
Early online date25 Jun 2016
DOIs
Publication statusPublished - Nov 2016

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