June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Neurosensory alterations in different mouse models of dry eye disease
Author Affiliations & Notes
  • Marina Zieger
    Center for Translational Ocular Immunology and Department of Ophthalmology, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, United States
  • Flavia Leao Barbosa
    Center for Translational Ocular Immunology and Department of Ophthalmology, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, United States
  • Brendan Kenyon
    Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Jun Mo
    Center for Translational Ocular Immunology and Department of Ophthalmology, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, United States
  • Deshea L Harris
    Center for Translational Ocular Immunology and Department of Ophthalmology, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, United States
  • Pedram Hamrah
    Center for Translational Ocular Immunology and Department of Ophthalmology, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, United States
    Cornea Service, New England Eye Center, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Marina Zieger None; Flavia Leao Barbosa None; Brendan Kenyon None; Jun Mo None; Deshea Harris None; Pedram Hamrah None
  • Footnotes
    Support  NIH-R01-EY022695, NIH-R01-EY026963 Tufts Institutional Support, Massachusetts Lions Eye Foundation and Tufts Medical Center Institutional Support, Research to Prevent Blindness Challenge Grant to the Department of Ophthalmology
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 711. doi:
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    • Get Citation

      Marina Zieger, Flavia Leao Barbosa, Brendan Kenyon, Jun Mo, Deshea L Harris, Pedram Hamrah; Neurosensory alterations in different mouse models of dry eye disease. Invest. Ophthalmol. Vis. Sci. 2023;64(8):711.

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

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Abstract

Purpose : Neurosensory abnormalities play etiological roles in dry eye disease (DED). Although several mouse models of DED are currently utilized, it is unclear if they develop distinct neurosensory dysfunctions. Our aim was to compare two common models of DED in terms of their neurosensory alterations.

Methods : Adult (n=10, per group) B6N female mice were exposed to desiccating stress in a chamber (C) with low humidity and air flow, or mice were exposed as described above and treated with 0.5 mg of scopolamine 3 times a day (C+S) for 14 days. The control group (CTL) was housed under normal conditions. The cornea surface was assessed by fluorescein staining and slit-lamp microscopy and tear volume was assessed by cotton thread test. Corneal nerve function was evaluated by esthesiometry and by behavioral nociceptor response to hyperosmolar saline. Cornea nerve density was quantified using ImageJ in anti-β III tubulin-labeled cornea whole-mounts imaged by confocal microscopy. Neurotrophin transcript levels were quantified by RT-qPCR and their protein levels measured by ELISA.

Results : Both models demonstrated clinical characteristics of the DED with decreased tear production and increase in corneal staining compared to CTL (p<0.0001). C+S mice had decreased corneal sensation (1.7±0.2) compared to C alone (4.1±0.4) or CTL (5.4±1) (p<0.0001). Nociceptive hypersensitivity increased in C+S (38.6±0.9) compared to C alone (28.5±0.5) or CTL (16.4±1.2) (p<0.001). Central and peripheral cornea nerve densities decreased in C+S (66.7±1.2 and 71.0±7.0, mm/mm2) compared to C alone (92.2±1.6 and 95.2±0.9) or CTL (117.0±3.2 and 123.8±5.8) (p<0.01). Gene expression decreased (p<0.05) in both models for neurotrophic growth factor (NGF; 3 and 2 fold), brain derived neurotrophic factor (3 and 1.5 fold), neurotrophin 3 (NT3; 3 fold and ns), neurotensin (4 and 2 fold), somatostatin (3 and 2 fold) and vasoactive intestinal peptide (2.5 and 2 fold) compared to CTL corneas. Levels of substance P (4 fold) and calcitonin gene-related peptide (3 fold) (p<0.01) only increased in C+S corneas. Protein levels of NGF and NT3 decreased in corneas and in trigeminal ganglia in both models (p<0.001).

Conclusions : Our study shows that the two models differ, with the C+S developing more severe neurosensory alterations, with decreased corneal nerve density and mechanosensation, increased hypersensitivity and reduced neurotrophin levels in cornea and in trigeminal ganglia.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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