July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
A Murine Model of Alzheimer’s Disease Shows Gender-Specific Ocular Surface Findings
Author Affiliations & Notes
  • Arsia Jamali
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Tomas Blanco
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Maria J Lopez
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Hamid-Reza Moein
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Deshea L Harris
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Victor G. Sendra
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Brendan Michael Kenyon
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Yashar Seyed-Razavi
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Selene Lomoio
    Alzheimer's Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Rachel Willen
    Alzheimer's Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Giuseppina Tesco
    Alzheimer's Disease Research Laboratory, Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Pedram Hamrah
    Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
    Cornea Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Arsia Jamali, None; Tomas Blanco, None; Maria Lopez, None; Hamid-Reza Moein, None; Deshea Harris, None; Victor Sendra, None; Brendan Kenyon, None; Yashar Seyed-Razavi, None; Selene Lomoio, None; Rachel Willen, None; Giuseppina Tesco, None; Pedram Hamrah, None
  • Footnotes
    Support  NIH-R01- EY022695 (PH), NIH-R21- EY025393 (PH), Tufts Medical Center Institutional Support (PH)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3321. doi:https://doi.org/
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      Arsia Jamali, Tomas Blanco, Maria J Lopez, Hamid-Reza Moein, Deshea L Harris, Victor G. Sendra, Brendan Michael Kenyon, Yashar Seyed-Razavi, Selene Lomoio, Rachel Willen, Giuseppina Tesco, Pedram Hamrah; A Murine Model of Alzheimer’s Disease Shows Gender-Specific Ocular Surface Findings. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3321. doi: https://doi.org/.

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

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Abstract

Purpose : The aim of this study is to evaluate ocular surface features in a mouse model of familial Alzheimer’s disease (FAD).

Methods : Corneal surface epithelium of 9-month-old female and male 5XFAD (FAD mouse model; mixed background) and wild-type (WT) littermates were evaluated clinically by fluorescein corneal staining (0-4 scores). Tear production was measured using phenol red thread and central corneal sensation was assessed using Cochet-Bonnet esthesiometer. Tear levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-17A were measured using Bioplex multiplex bead assay. Corneal nerve density was measured on confocal micrographs of whole-mounted corneas stained with βIII-tubulin, using NeuronJ plugin for ImageJ. T-test was used to assess statistical significance. P<0.05 was considered significant.

Results : While female 5XFAD mice demonstrated significantly higher corneal fluorescein staining score (3.0±0.8) compared to female controls (0.5±0.6; p=0.002), no significant difference was observed between male 5XFAD (1.0±0.8) and male control mice (0.2+0.5; p=0.16). Similarly, although we observed significantly lower tear production in female 5XFAD mice (1.5±0.7 mm) vs. controls (6.6±1.1 mm; p=0.004), we did not observe significant difference in males (4.5±0.7 vs. 4.3±1.4 mm; p=0.18). In addition, we observed significantly reduced corneal sensation in female 5XFAD mice (3.2±0.3 cm) compared with controls (5.7±0.5 cm; p=0.003) mice, as well as in male 5XFAD mice (4.7±0.3 cm) compared with male controls (5.6±0.4 cm; p=0.03), although the decrease in male mice was not as pronounced. Similarly, we observed decreased corneal nerve density in both female and male 5XFAD mice in the corneal periphery compared with controls (104.6±14.0 vs. 130.5± 8.1 mm/mm2; p=0.03 and 102.8 ±5.7 vs. 127.7±7.4 mm/mm2; p=0.002). Female 5XFAD mice showed higher levels of TNF-α (125.7±26.8 pg/mL), IFN-γ (5.5±1.0 pg/mL), and IL-17A (14.6±2.1 pg/mL) in their tears compared to controls (55.1±3.5 pg/mL; p=0.01, 3.8±0.6 pg/mL; p=0.02, and 4.5±5.1 pg/mL; p=0.01, respectively). However, we did not detect significant differences in the tear levels of TNF-α, IFN-γ, and IL-17A between 5XFAD male mice and controls (p>0.05).

Conclusions : FAD is associated with ocular surface disease including reduced nerve density and enhanced tear inflammatory cytokine levels that is more prominent in females.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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