July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Substance P Modulation of Human and Murine Corneal Neovascularization
Author Affiliations & Notes
  • Giulio Ferrari
    Ophthalmology -Cornea Unit-Eye Repair, OSPEDALE SAN RAFFAELE, Milan, Italy
  • Marco Barbariga
    Ophthalmology -Cornea Unit-Eye Repair, OSPEDALE SAN RAFFAELE, Milan, Italy
  • Philippe Fonteyne
    Ophthalmology -Cornea Unit-Eye Repair, OSPEDALE SAN RAFFAELE, Milan, Italy
  • Fabio Bignami
    Ophthalmology -Cornea Unit-Eye Repair, OSPEDALE SAN RAFFAELE, Milan, Italy
  • Paolo Rama
    Ophthalmology -Cornea Unit-Eye Repair, OSPEDALE SAN RAFFAELE, Milan, Italy
  • Footnotes
    Commercial Relationships   Giulio Ferrari, patent ID: PCT/EP2012/063067 (P); Marco Barbariga, None; Philippe Fonteyne, None; Fabio Bignami, None; Paolo Rama, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3336. doi:
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    • Get Citation

      Giulio Ferrari, Marco Barbariga, Philippe Fonteyne, Fabio Bignami, Paolo Rama; Substance P Modulation of Human and Murine Corneal Neovascularization
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):3336.

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

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Abstract

Purpose : To investigate the role of Substance P (SP) in patients affected with corneal neovascularization (CNV) and in three different Tac1-Knockout murine models of CNV.

Methods : Substance P level in tears was measured with a multiplex bead assay. The extent of human CNV was quantified as number of affected corneal quadrants. Murine CNV was induced in both strains by means of: total disepithelization, alkali burn and intra-stromal sutures. After sacrifice, CNV (blood and lymphatic) and leukocyte infiltration were quantified by CD31, LYVE1, and CD45 immunofluorescence, respectively. Trigeminal ganglions were collected for qPCR IL1β quantification. Hematoxylin-eosin corneal cross sections and whole-mounted β-3-tubulin nerve staining were used to compare anatomy and nerve density of WT vs Tac1-KO normal mice.

Results : SP tear levels correlate positively with CNV extension in patients (r=0.49, p=0.03). After disepithelization,Tac1-KO corneas showed reduced blood and lymphatic vascularization (-34% and -51% respectively) as compared to the WT counterpart. CD45+ leukocytes infiltrating the cornea were reduced in Tac1-KO mice as opposed to WT in the disepithelization (p=0.0001), alkali burn (p=0.0258), and suture (p=0.0149) models. Tac1-KO mice showed reduced IL1β expression in the trigeminal ganglion. Normal WT and Tac1-KO corneas did not show significant differences in transparency, thickness, and nerve density.

Conclusions : Our results suggest: (i) the involvement of substance P in human CNV; (ii) the key role of SP in promoting inflammatory CNV in three different mouse models; and (iii) that absence of SP is not associated with obvious ocular surface pathology in a KO model.

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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