June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Early neuroinflammatory responses in the visual pathway in a feline inherited glaucoma model
Author Affiliations & Notes
  • Kazuya Oikawa
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
    Surgical Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Julie Kiland
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Virginia Mathu
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Odalys Torne
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
    Surgical Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Gillian J McLellan
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
    Surgical Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Kazuya Oikawa None; Julie Kiland None; Virginia Mathu None; Odalys Torne None; Gillian McLellan None
  • Footnotes
    Support  NIH Grants R01 EY027396 and P30 EY016665; BrightFocus Foundation National Glaucoma Research Award; McPherson Eye Research Institute Kenzi Valentyn grant; unrestricted award to the UW-Madison Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 13. doi:
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    • Get Citation

      Kazuya Oikawa, Julie Kiland, Virginia Mathu, Odalys Torne, Gillian J McLellan; Early neuroinflammatory responses in the visual pathway in a feline inherited glaucoma model. Invest. Ophthalmol. Vis. Sci. 2022;63(7):13.

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

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Abstract

Purpose : Myeloid cell activation has been implicated in glaucoma pathogenesis in humans and animal models. The purpose of the study is to delineate early myeloid cell activation in an inherited feline model of glaucoma.

Methods : Retinal, optic nerve head (ONH) and distal optic nerve (ON) tissues from 8 juvenile 10-12 week-old cats (4 males and 4 females) with feline congenital glaucoma (FCG) and 5 age-matched normal control cats (3 males and 2 females) were used. Data for weekly intraocular pressure (IOP) and optic nerve axon counts were available for all subjects. Protein and gene expression in tissue cryosections were examined by immunofluorescence labeling (IF) and RNAscope in situ hybridization (ISH), respectively. Retinal tissue was IF labeled for myeloid cell marker, IBA-1 and flat-mounted. ISH for markers of infiltrating monocytes/macrophages (CCR2) and proinflammatory cytokines (IL1A, C1QA, TNF) was performed. Microglia were identified by IF of homeostatic microglial marker, P2RY12. Microscopy images wereanalyzed using Image J, QuPath and Imaris. Two-tailed unpaired t-test or Mann-Whitney test or ANOVA were used for between-group comparisons (p<0.05 considered significant).

Results : Mean IOP [SEM] was higher in FCG (19.4 mmHg [3.1]) than age-matched controls (13.5 mmHg [1.8]) (p<0.001). Profound microgliosis was observed in the retina and ONH in juvenile FCG cats (no detectable axon damage) compared to age-matched controls (p<0.01) whereas ON myeloid cell density was not significantly different between groups. The density of CCR2+ infiltrating monocytes was increased in ONHs in FCG relative to controls. While C1QAwas ubiquitously expressed in myeloid cells, only small subsets expressed IL1A or TNF in FCG. The majority of IBA1+ myeloid cells in the retina, ON and prelaminar ONH are positive for P2RY12 in cats, but loss of P2RY12 expression was identified in the retrolaminar region of the ONH in FCG. Myeloid cells in the FCG retina were more morphologically heterogeneous than normal, ranging from ameboid to hypertrophic, with reduced complexity of myeloid cell processes.

Conclusions : Activation of myeloid cells in early-stage FCG is characterized by a subset of proinflammatory myeloid cells, infiltrating monocytes and morphological remodeling in the retina and ONH.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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