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Eleni Beli, Sergio Li Calzi, Yaqian Duan, Sergio Caballero, Julia V Busik, Maria B Grant; Spleen as a source for myeloid cells infiltrating the diabetic retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2507.
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© ARVO (1962-2015); The Authors (2016-present)
Leukocyte infiltration in the diabetic retinas has been described in both clinical and experimental settings, but their source, phenotype and role of these cells in the progression of diabetic retinopathy is not clear. We asked whether the spleen is a source of leukocyte infiltration in the retina, and how diabetes affects leukocyte recruitment.
Retinal ischemia reperfusion (I/R) model was used in sham-operated and splenectomized C57BL/6 mice. Flow cytometry was performed in the retinas 24hrs post I/R and the phenotype of infiltrating cells was examined. The content of myeloid cells in the spleen of STZ-diabetic mice (4 months of diabetes) was examined at ZT5 (day) and ZT17 (night) of a day/night cycle (ZT= Zeitgeber Time; hrs after the lights go on). I/R was conducted at ZT5 and ZT17 to examine how the myeloid content of the spleen affects the recruitment of myeloid cells into the retina of diabetic and control animals.
I/R induced significant infiltration of CD45hi CD11b+ myeloid cells (neutrophils, macrophages and monocytes) into the retina. The level of infiltration was reduced significantly in splenectomized mice, suggesting that the spleen is a major source of recruited leukocytes. Under normal diurnal conditions the diabetic mice had increased Ly6Chi splenic monocyte content at ZT17. When I/R was induced at that time, the infiltration of myeloid cells in the retina was also significantly increased compared to controls, who had fewer Ly6Chi monocytes at that time.
We show that splenic monocytes are recruited in the retina after ischemic injury and that the content of splenic myeloid cells correlates with the level of infiltrating cells. These results put the spleen on the spotlight for targeting diabetic complications.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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