School of Biomedical Sciences - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/57545

Filters

2022 - 2023 2
2
Reset filters

Settings
Statistics
Citations
Author: Wilkinson-Berka, Jennifer × Start date: 2020 × End date: 2023 ×

Search Results

Now showing 1 - 2 of 2
  • Item
    Thumbnail Image
    Early Depletion of Neutrophils Reduces Retinal Inflammation and Neovascularization in Mice with Oxygen-Induced Retinopathy
    Deliyanti, D ; Suphapimol, V ; Ang, P ; Tang, X ; Jayasimhan, A ; Wilkinson-Berka, JL (MDPI, 2023-11)
    Retinal inflammation is a central feature of ocular neovascular diseases such as diabetic retinopathy and retinopathy of prematurity, but the contribution of neutrophils to this process is not fully understood. We studied oxygen-induced retinopathy (OIR) which develops in two phases, featuring hyperoxia-induced retinal vaso-obliteration in phase I, followed by retinal neovascularization in phase II. As neutrophils are acute responders to tissue damage, we evaluated whether neutrophil depletion with an anti-Ly6G mAb administered in phase I OIR influenced retinal inflammation and vascular injury. Neutrophils were measured in blood and spleen via flow cytometry, and myeloperoxidase, an indicator of neutrophil activity, was evaluated in the retina using Western blotting. Retinal vasculopathy was assessed by quantitating vaso-obliteration, neovascularization, vascular leakage, and VEGF levels. The inflammatory factors, TNF, MCP-1, and ICAM-1 were measured in retina. In the OIR controls, neutrophils were increased in the blood and spleen in phase I but not phase II OIR. In OIR, the anti-Ly6G mAb reduced neutrophils in the blood and spleen, and myeloperoxidase, inflammation, and vasculopathy in the retina. Our findings revealed that the early rise in neutrophils in OIR primes the retina for an inflammatory and angiogenic response that promotes severe damage to the retinal vasculature.
  • Item
    Thumbnail Image
    Tetraspanin CD82 restrains phagocyte migration but supports macrophage activation
    McGowan, ENS ; Wong, O ; Jones, E ; Nguyen, J ; Wee, J ; Demaria, MC ; Deliyanti, D ; Johnson, CJ ; Hickey, MJ ; McConville, MJ ; Wilkinson-Berka, JL ; Wright, MD ; Binger, KJ (CELL PRESS, 2022-07-15)
    Phagocytes migrate into tissues to combat infection and maintain tissue homeostasis. As dysregulated phagocyte migration and function can lead to inflammation or susceptibility to infection, identifying molecules that control these processes is critical. Here, we show that the tetraspanin CD82 restrains the migration of neutrophils and macrophages into tissues. Cd82 -/- phagocytes exhibited excessive migration during in vivo models of peritoneal inflammation, superfusion of CXCL1, retinopathy of prematurity, and infection with the protozoan parasite L. mexicana. However, with the latter, while Cd82 -/- macrophages infiltrated infection sites at higher proportions, cutaneous L. mexicana lesions were larger and persisted, indicating a failure to control infection. Analyses of in vitro bone-marrow-derived macrophages showed CD82 deficiency altered cellular morphology, and impaired gene expression and metabolism in response to anti-inflammatory activation. Altogether, this work reveals an important role for CD82 in restraining phagocyte infiltration and mediating their differentiation in response to stimulatory cues.