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Dean Talia, Tong Zhu, Alex Agrotis, Robyn Slattery, Melanie Le Page, Fabienne Mackay-Fisson, Jennifer Wilkinson-Berka; The contribution of T cells to retinopathy of prematurity in mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2027.
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Inflammation is known to contribute to the vascular pathology which develops in retinopathy of prematurity (ROP). Previous studies have indicated a causative role for the adaptive immune system in ROP; however the mechanisms by which this occurs are unknown. We evaluated the contribution of T and B cells to experimental ROP using mice deficient in these cell populations.
RAG-1-/- mice (T and B cell deficient) and MuMT-/- mice (T cell sufficient, B cell deficient) were studied and comparisons made to C57BL/6 mice. ROP was induced by exposure to 75% oxygen from postnatal day (P) 7 to P12 and room air until P13 (acute ROP) or P18 (established ROP). Control mice were in room air from birth until P13 or P18. Neovascularization and the area of the central avascular retina were quantitated in retinal wholemounts using ImageJ (NIH, USA). Flow cytometry was used to determine the number and percentage of T cells, B cells and dendritic cells in the spleen and pooled lymph nodes. The distribution and number of CD3+ T cells were evaluated in retinal wholemounts using immunofluorescence.
Retinal neovascularizaion was reduced in RAG-1-/- ROP mice, but not in MuMT-/- ROP mice compared to C57BL/6 ROP controls, suggesting a predominant role for T cells in ROP. FACS analysis revealed an approximately 3.6-fold increase in CD4+CD25+Foxp3+ Tregs in the spleens of C57BL/6 ROP mice at P13 compared to room air controls (p>0001). By P18 the number of CD4+CD25+Foxp3+ Tregs in spleen and lymph nodes had declined, whilst the number of CD8+ T cells increased approximately 6.5-fold compared to room air controls (P>0.0001). Immunolabelling for CD3+ T cells was increased in C57BL/6 ROP retina at P18 compared to room air controls and was located adjacent to the vasculature.
Particular populations of T cells may contribute to the development of ROP, suggesting the potential role of immune-based therapies for treatment of the disorder.
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