July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
A novel protective role of the C-type lectin Mincle in modulating inflammation and lesion size a mouse model of choroidal neovascularization.
Author Affiliations & Notes
  • Matt Rutar
    The University of Melbourne, Melbourne, Victoria, Australia
  • Alice Brandli
    The University of Melbourne, Melbourne, Victoria, Australia
  • Gene Venables
    The University of Melbourne, Melbourne, Victoria, Australia
  • Erica L Fletcher
    The University of Melbourne, Melbourne, Victoria, Australia
  • Christine Wells
    The University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Matt Rutar, None; Alice Brandli, None; Gene Venables, None; Erica Fletcher, None; Christine Wells, None
  • Footnotes
    Support  National Health and Medical Research Council (NHMRC), Australia
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 988. doi:https://doi.org/
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      Matt Rutar, Alice Brandli, Gene Venables, Erica L Fletcher, Christine Wells; A novel protective role of the C-type lectin Mincle in modulating inflammation and lesion size a mouse model of choroidal neovascularization.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):988. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Neovascular 'wet' AMD is thought to be influenced by changes in macrophage recruitment and polarisation. Mincle is a C-type lectin that acts as a pattern recognition receptor for an array of pathogens and damage-associated motifs, and previously described to augment myeloid cell recruitment and activation. However, mincle signalling is poorly documented in nervous system injury. Here, we investigated a role of mincle in experimental model of choroidal neovascularization (CNV).

Methods : Laser photocoagulation (350 mW) was used to induced CNV lesions in isogenic Wt and Mincle KO mice (n= 10-12 eyes/group). Leakage was assessed at 2 and 7 days post-laser using both fluorescence angiography, and CNV lesion height ratio on trichrome stained retinal sections; data were quantified using image J. mRNA expression profiling and flow cytometry were also performed on both retina and RPE/Choroid. After CNV, mice were euthanised and retinas and RPE/Choroid were micro-dissected from each other and assessed. mRNA expression levels were compared using qPCR arrays for C-type lectins and associated cytokines (n=10), while 10-color flow cytometry was performed to profile myeloid populations (n=5). Statistical significance was determined using ANOVA with Tukey’s post-hoc test.

Results : Expression analysis revealed increases in C-type lectins including Mincle, MCL, Dectin1, and Dectin2 in choroid – but not retina – over the time-course following CNV (P<0.05). Of note, Mincle expression increased sharply by 2-days post-CNV (P<0.05), and correlated with increases in Ccl2, Ccl3, Ccl4, and Cxcl2 (P<0.05). CNV lesion size was increased significantly in the Mincle KO cohort by over 30% percent at 2 Days, and over 45% by 7 days (both P<0.05). Cytometric analysis of myeloid populations in the choroid indicated significantly decreased proportions of inflammatory monocytes (Ly6c-Hi) and recruited macrophages (ly6c-lo, MHCII-hi), but not neutrophils (Ly6g+) or DCs (CD11c-hi, MHCII-hi) at 2 and 7 days in Mincle KO mice, relative to controls (P<0.05).

Conclusions : Our findings point to a novel role for Mincle signalling in shaping inflammatory responses in the choroid, specifically the recruitment polarisation of monocyte and macrophage subsets in CNV. These data suggest a mechanism for mincle in the pathogenesis of wet AMD, and its modulation as a potential treatment target.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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