CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes.
CX3CR1 deficiency accelerates the development of retinopathy in a rodent model of type 1 diabetes.
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DOI：
10.1007/s00109-016-1433-0
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发表时间：
2016-11
影响因子：
4.7
通讯作者：
Grant, Maria B.
中科院分区：
文献类型：
--
作者：
Beli, Eleni;Dominguez, James M., II;Hu, Ping;Thinschmidt, Jeffrey S.;Caballero, Sergio;Li Calzi, Sergio;Luo, Defang;Shanmugam, Sumathi;Salazar, Tatiana E.;Duan, Yaqian;Boulton, Michael E.;Mohr, Susanna;Abcouwer, Steven F.;Saban, Daniel R.;Harrison, Jeffrey K.;Grant, Maria B.
本研究探讨了CX3CR1在糖尿病视网膜病变（DR）进展中的作用。比较了野生型（WT）、CX3CR1空型（CX3CR1gfp/gfp， KO）和杂合型（CX3CR1+/gfp, Het）小鼠视网膜在链脲佐菌素（STZ）诱导的糖尿病存在和不存在情况下的差异。在糖尿病患者4个月时，STZ-KO中CX3CR1的缺乏增加了血管病理，因为只有在STZ-KO组中观察到脱细胞毛细血管的显著增加。CX3CR1缺乏和糖尿病对视网膜神经退行性变有相似的影响，通过增加DNA片段来测量。STZ-KO小鼠视网膜血管病变与视网膜单核细胞源性巨噬细胞数量增加有关。此外，与STZ-WT相比，STZ-KO小鼠骨髓中炎症单核细胞数量增加，单核细胞向脾脏的归巢受损。糖尿病诱导的视网膜IL-10表达在KO小鼠中明显减少，当KO小鼠的骨髓源性巨噬细胞维持在高糖状态时，它们对LPS刺激的IL-10表达明显减少，TNF-α表达明显增加。这些发现支持CX3CR1缺失通过增加促炎髓样细胞的募集来加速DR血管病理的发展，而促炎髓样细胞表现出抗炎IL-10的表达减少。
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. 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.
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影响因子：
4.4
作者：
Kezic, Jelena Marie;Chen, Xiangting;McMenamin, Paul G.
通讯作者：
McMenamin, Paul G.
影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
影响因子：
4.4
作者：
Abcouwer, Steven F.;Lin, Cheng-mao;Antonetti, David A.
通讯作者：
Antonetti, David A.
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
DOI：
10.1111/nyas.12805
发表时间：
2015-01-01
期刊：
NEUROIMMUNOMODULATION IN HEALTH AND DISEASE
影响因子：
--
作者：
Lauro, Clotilde;Catalano, Myriam;Limatola, Cristina
通讯作者：
Limatola, Cristina