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Devy Deliyanti, William Figgett, Dean Michael Talia, Jennifer L Wilkinson-Berka; CD8+ T Lymphocytes Contribute to the Development of Neovascularization in Ischemic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2558.
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Retinal neovascularization is a major cause of vision loss and blindness and the hallmark feature of ocular neovascular diseases such as retinopathy of prematurity and diabetic retinopathy. The development of retinal neovascularization is often preceded by an inflammatory response to tissue damage characterized by the activation of resident immune cells such as microglia. This event is followed by the infiltration of other immune cell populations, such as monocytes and neutrophils. CD8+ T lymphocytes have strong pro-inflammatory effects in various sites of tissue damage, yet their role in retinal neovascularization is not fully understood.
The mouse oxygen-induced retinopathy (OIR) model was used. Postnatal day (P)7 C57BL/6J and RAG-1 KO mice were exposed to 75% oxygen for 5 days and then to room air until P18. Lectin-stained retinal wholemounts were used to assess the extent of neovascularization (NV) and vaso-obliteration (VO). Flow cytometry was used to measure the number of T cells in the retina and lymphoid organs.
In the retina of C57Bl/6 mice with OIR, flow cytometry revealed that CD8+ T cells were increased in greater numbers compared to CD4+ T cells. CD8+ T cell depletion but not CD4+ T cell depletion using monoclonal antibodies, reduced retinal NV and VO in OIR. Furthermore, vascular leakage and VEGF were also reduced in the retina of OIR mice treated with the CD8 depletion antibody but not with the CD4 depletion antibody. To further study CD8+ T cells, RAG-1 KO mice which lack this cell population were evaluated, and were found to be protected from OIR-induced retinal vasculopathy and inflammation. To confirm that these effects were CD8+ T cell-dependent, CD8+ T cells were adoptively transferred into RAG-1 KO mice with OIR. This approach restored retinal NV and VO, and also increased retinal VEGF levels as well as vascular leakage. The adoptive transfer of CD8+ T cells into RAG-1 KO mice with OIR partially reconstituted CD8+ T cells in lymphoid tissues and CD8+T cells infiltrated into the retina. Flow cytometry of lymphoid organs revealed that CD8+ T cells are increased in lymphoid organs of OIR mice in the early phase of the disease and infiltrate the retina as the development of neovascularization is established.
CD8+ T cells promote the development of neovascularization in ischemic retinopathy by augmenting the inflammatory response in the retina.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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