CX3CR1 deficiency accelerates the development of retinopathy in a rodent model
of type 1 diabetes.
Authors 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
Submitted By Steven Abcouwer on 7/26/2016
Status Published
Journal Journal of molecular medicine (Berlin, Germany)
Year 2016
Date Published 6/1/2016
Volume : Pages Not Specified : Not Specified
PubMed Reference 27344677
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
(CX3CR1(gfp/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-a 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., • 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-a and
less IL-10. • The role of IL-10 in protection from progression of DR is