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Eleni Beli, Svetlana Bozack, Harshini Chakravarthy, Qi Wang, Nermin Kady, Tatiana Salazar, James M Dominguez, Ashay D Bhatwadekar, Maria Grant, Julia V Busik; Spleen as the source of infiltrating monocytes in the diabetic retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4907. doi: https://doi.org/.
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We have previously identified that increased infiltration of inflammatory monocytes contributes to retinal pathology in diabetes. Moreover, diurnal fluctuations of monocytes in both rodents and humans with type 1 diabetes (T1D) are altered and diabetes results in an increase in peak release as well as a phase shift of circulating monocytes compared to age-matched controls. In this study, we asked if the spleen has a role in regulating monocyte phenotype and trafficking thus contributing to the pathogenesis of diabetic retinopathy.
Control (n=4) and 4 months STZ diabetic (n=4) mice were euthanized at ZT4-16. Single cell suspensions from spleen, retina, bone marrow and blood were analyzed by flow cytometry. Patrolling monocytes were identified as GR1(1A8)-, CD3-, CD19-, NK1.1-, CD11b+, CD115+, F480-, Ly6Clo cells. Inflammatory monocytes were identified as GR1-, CD3-, CD19-, NK1.1-, CD11b+, F480-, CD115+, Ly6Chi cells.
The levels of monocytes in the peripheral circulation were reduced from 49,064 ± 14,051 to 2,742 ± 834 (p=0.03) between ZT4 and ZT13 concurrent with an increase in adhesion molecules expression in the retina: CCL2 mRNA expression changed from 0.023 ± 0.01 at ZT4 to 0.011 ± 0.00 at ZT13 (p=0.051) and VCAM mRNA expression from 0.035 ± 0.01 at ZT4 to 0.14 ± 0.01 at ZT13 (p< 0.05). Both patrolling and inflammatory monocytes were decreased in the spleen at the active phase (ZT16). Patrolling monocytes accumulated in the bone marrow during the active phase, while the inflammatory monocytes increased in the circulation in diabetic, but not control animals.
Monocytes released from spleen may be an important source of infiltrating inflammatory monocytes in the retina contributing to the pathogenesis of diabetic retinopathy.
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