Abstract
Purpose :
We have recently demonstrated the presence of plasmacytoid dendritic cells (pDCs) in murine retina. In particular we have shown that pDCs are in close proximity to retinal vessels. Thus, we aimed to evaluate whether resident pDCs may mediate the homeostasis of retinal vasculature in the laser-induced choroidal neovascularization (CNV) mice model of age-related macular degeneration.
Methods :
Six- to 8-week-old, BDCA2-DTR mice were intraperitoneally injected with 200 mg/ml of diphtheria toxin or PBS as pDC-depleted and sham-depleted animals respectively. pDC-depletion was corroborated by flow cytometry. Both naïve and laser-induced CNV depleted animals were evaluated in this study. CNV was performed on the same day of depletion. Three and 7 days after CNV induction, fluorescein angiography was conducted in sham and pDC-depleted animals. Fundus images were obtained; abnormal vascular leakage and scar size were quantified as fluorescence intensity and scar area (as normalized to optic disc) respectively. Further, we used our transgenic DPE-GFP×RAG-1-/- mice in which only pDCs express GFP, to quantify retinal GFP cells in naïve and after laser-induced CNV.
Results :
Fluorescein angiography in naïve animals showed that vascular leakage was 1.5-fold (p<0.001) and 1.4-fold (p=0.042) increased after 3 and 7 days of pDC-depletion, respectively, compared with sham depleted. At 7 days after CNV induction, vascular leakage and scar area increased 4-fold (p=0.040) and 2-fold (p=0.046), respectively, in pDC-depleted animals. Additionally, retinal eGFP cells were CD11clow, PDCA-1+, Ly6C+, Ly49Q+ and CD19—, CD3—, F4/80—, CD11b—. This population was increased 4-fold after laser-induced CNV as measured by flow cytometry and epi-fluorescent microscopy (p<0.001).
Conclusions :
pDCs are required to preserve vasculature homeostasis in naïve retinas. Moreover, pDC depletion in a clinically relevant model of AMD exhibits worse outcomes, including increased vascular leakage and scar size, indicating that pDCs may be necessary to limit disease.
This is a 2021 ARVO Annual Meeting abstract.