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

Publication ,  Journal Article
Beli, E; Dominguez, JM; Hu, P; Thinschmidt, JS; Caballero, S; Li Calzi, S; Luo, D; Shanmugam, S; Salazar, TE; Duan, Y; Boulton, ME; Mohr, S ...
Published in: J Mol Med (Berl)
November 2016

UNLABELLED: 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. KEY MESSAGES: • CX3CR1 deletion in STZ-diabetic mice accelerated the onset of diabetic retinopathy (DR). • The early onset of DR was associated with increased retinal cell apoptosis. • The early onset of DR was associated with increased recruitment of bone marrow-derived macrophages to the retina. • Bone marrow-derived macrophages from CX3CR1 KO diabetic mice expressed more TNF-α and less IL-10. • The role of IL-10 in protection from progression of DR is highlighted.

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Published In

J Mol Med (Berl)

DOI

EISSN

1432-1440

Publication Date

November 2016

Volume

94

Issue

11

Start / End Page

1255 / 1265

Location

Germany

Related Subject Headings

  • Streptozocin
  • Retina
  • RNA, Messenger
  • Myeloid Cells
  • Monocytes
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Macrophages
  • Interleukin-10
  • Inflammation Mediators
 

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Beli, E., Dominguez, J. M., Hu, P., Thinschmidt, J. S., Caballero, S., Li Calzi, S., … Grant, M. B. (2016). CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes. J Mol Med (Berl), 94(11), 1255–1265. https://doi.org/10.1007/s00109-016-1433-0
Beli, Eleni, James M. Dominguez, Ping Hu, Jeffrey S. Thinschmidt, Sergio Caballero, Sergio Li Calzi, Defang Luo, et al. “CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes.J Mol Med (Berl) 94, no. 11 (November 2016): 1255–65. https://doi.org/10.1007/s00109-016-1433-0.
Beli E, Dominguez JM, Hu P, Thinschmidt JS, Caballero S, Li Calzi S, et al. CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes. J Mol Med (Berl). 2016 Nov;94(11):1255–65.
Beli, Eleni, et al. “CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes.J Mol Med (Berl), vol. 94, no. 11, Nov. 2016, pp. 1255–65. Pubmed, doi:10.1007/s00109-016-1433-0.
Beli E, Dominguez JM, Hu P, Thinschmidt JS, Caballero S, Li Calzi S, Luo D, Shanmugam S, Salazar TE, Duan Y, Boulton ME, Mohr S, Abcouwer SF, Saban DR, Harrison JK, Grant MB. CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes. J Mol Med (Berl). 2016 Nov;94(11):1255–1265.
Journal cover image

Published In

J Mol Med (Berl)

DOI

EISSN

1432-1440

Publication Date

November 2016

Volume

94

Issue

11

Start / End Page

1255 / 1265

Location

Germany

Related Subject Headings

  • Streptozocin
  • Retina
  • RNA, Messenger
  • Myeloid Cells
  • Monocytes
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Macrophages
  • Interleukin-10
  • Inflammation Mediators