April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Reciprocal Inhibition of Nerves and Neovessels in the Cornea
Author Affiliations & Notes
  • Amir R. Hajrasouliha
    Ophthalmology, Schepens Eye Research Institute, Boston, Massachusetts
  • Giulio Ferrari
    Ophthalmology, Bietti Eye Foundation, Rome, Italy
  • Hiroki Ueno
    Ophthalmology, Schepens Eye Research Institute, Boston, Massachusetts
  • Zahra Sadrai
    Ophthalmology, Schepens Eye Research Institute, Boston, Massachusetts
  • Paolo Rama
    Cornea and Ocular surface Unit, San Raffaele Scientific Foundation, Milan, Italy
  • Reza Dana
    Ophthalmology, Schepens Eye Research Institute, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  Amir R. Hajrasouliha, None; Giulio Ferrari, None; Hiroki Ueno, None; Zahra Sadrai, None; Paolo Rama, None; Reza Dana, None
  • Footnotes
    Support  RO1EY12963; RO1EY19098
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6430. doi:
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      Amir R. Hajrasouliha, Giulio Ferrari, Hiroki Ueno, Zahra Sadrai, Paolo Rama, Reza Dana; Reciprocal Inhibition of Nerves and Neovessels in the Cornea. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6430.

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Abstract

Purpose: : To study the interaction between corneal nerves and neovessels in the cornea.

Methods: : Corneal angiogenesis was induced using a b-FGF micropellet (40ng) implanted in the cornea of 6 week-old C57/BL6 male mice (n = 7). After 7 days, corneas were excised and stained for beta-3 tubulin, as a marker for nerves, and PECAM (CD31), as a marker for blood vessels. A second group of C57/BL6 mice (n = 7) underwent Trigeminal Stereotactic Electrolysis, a validated procedure to surgically remove corneal nerves. After 7 days, corneas were removed and either immunostained for PECAM and beta-3 tubulin or the expression levels of VEGF-R3 and PEDF were evaluated using RT-PCR.

Results: : In the angiogenesis model, the nerves were completely absent at the site of neovessel formation both in deep and superficial stromal layer with intact nerves elsewhere. On the other hand, in the denervated corneas using Trigeminal Stereotactic Electrolysis we observed ingrowth of blood vessels in conjuction with significant reduction in VEGFR-3 (52%, P= 0.007) and PEDF (56%, P=0.012) expression levels.

Conclusions: : We show preliminary evidence that demonstrates the inverse correlation between nerves and blood vessels in the cornea. We showed this morphologically with immunohistochemistry and at the transcription level following denervation, with the detection of a significant decrease of two potent angiostatic molecules (PEDF and VEGF-R3) normaly present at the cornea. As a consequence, it can be inferred that normal corneal innervation is instrumental to corneal avascularity by maintaining the level of angistatic molecules. This is a frequent observation in the clinic, as corneal neovascularization is a common complication of end-stage neurotrophic keratopathy, a disease caused by corneal nerve loss.

Keywords: neovascularization • vascular endothelial growth factor • innervation: neural regulation 
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