September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Lack of neurokinin-1 receptor alters the homeostasis of ocular surface and causes an early development of herpes stromal keratitis
Author Affiliations & Notes
  • Subhash Gaddipati
    Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan, United States
    Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Pushpa Rao
    Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Andrew Jerome
    Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Bala Bharathi Burugula
    Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan, United States
    Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Susmit Suvas
    Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan, United States
    Anatomy & Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Subhash Gaddipati, None; Pushpa Rao, None; Andrew Jerome, None; Bala Bharathi Burugula, None; Susmit Suvas, None
  • Footnotes
    Support  EY022417, EY004068, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Subhash Gaddipati, Pushpa Rao, Andrew Jerome, Bala Bharathi Burugula, Susmit Suvas; Lack of neurokinin-1 receptor alters the homeostasis of ocular surface and causes an early development of herpes stromal keratitis. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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

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Abstract

Purpose : Neurokinin-1 receptor (NK1R) is the highest affinity receptor for substance P (SP), an eleven amino acid long neuropeptide present in the tear film and in sensory nerve fibers innervating the corneal epithelium. The purpose of this study is to determine the outcome of NK1R deficiency on ocular surface homeostasis and development of herpes stromal keratitis (HSK) in mouse model.

Methods : The corneal flat mounts from uninfected C57BL/6 (B6) and NK1R-/- mice were stained for dendritic cells, corneal nerves and adhesion proteins, and visualized under confocal microscope. Phenol red thread test was carried out to measure the volume of unstimulated tears in both groups of mice. BrdU single pulse labeling was carried out to determine the proliferative index of corneal epithelial cells. After ocular HSV-1 infection, the development of corneal opacity and angiogenesis was determined in both groups using slit lamp. Flow cytometery was carried out on draining lymph nodes (DLN) and corneal samples from infected groups of mice at different time-points post-infection.

Results : A significant decrease in the numbers of CD11c+ cells with dendritic processes was noted in the corneal epithelium of unmanipulated NK1R-/- than B6 mice. In addition, reduced corneal sub-epithelial nerve branching, sub-basal plexus leash numbers and patchy E-cadherin staining were detected in the corneal epithelium of NK1R-/- mice. BrdU labeling index for uninjured corneal epithelium was higher in NK1R-/- mice. NK1R-/- mice also showed significantly reduced volume of basal surface tear. Interestingly, naïve NK1R-/- mice showed a dramatic increase in the numbers of CD11c+ cells near the limbal region. After ocular HSV-1 infection, the numbers of CD11c+DCs infiltrating the infected corneas and then migrating to the DLN were significantly higher in NK1R-/- than B6 mice, when measured at early time-point after infection. This resulted into an early generation of larger numbers of IFN-g secreting virus specific CD4 T cells, which migrated to the inflamed corneas and caused an early development of severe HSK in NK1R-/- mice.

Conclusions : Together, our results showed the role of NK1R signaling in regulating corneal epithelial mitotic activity, adhesion, corneal nerve density, tear volume, homeostasis of corneal dendritic cells and the development of HSK.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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