CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes.
J Mol Med (Berl)
; 94(11): 1255-1265, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-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 (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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
4_aids
/
6_cardiovascular_diseases
/
6_diabetes
/
6_endocrine_disorders
/
6_obesity
Asunto principal:
Diabetes Mellitus Tipo 1
/
Retinopatía Diabética
/
Receptor 1 de Quimiocinas CX3C
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Mol Med (Berl)
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos