Nerves and neovessels inhibit each other in the cornea

Giulio Ferrari, Amir R. Hajrasouliha, Zahra Sadrai, Hiroki Ueno, Sunil K. Chauhan, Reza Dana

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

PURPOSE. To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea. METHODS. b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epitheliumderived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining. RESULTS. No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5% reduction, P = 0.001) and PEDF protein expression (64% reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed. CONCLUSION. Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis.

Original languageEnglish (US)
Pages (from-to)813-820
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Cornea
Electrolysis
Blood Vessels
Denervation
Corneal Neovascularization
CD31 Antigens
Trigeminal Nerve
Tubulin
Growth
Fluorescent Antibody Technique
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Macrophages
Staining and Labeling
Polymerase Chain Reaction
Proteins

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Nerves and neovessels inhibit each other in the cornea. / Ferrari, Giulio; Hajrasouliha, Amir R.; Sadrai, Zahra; Ueno, Hiroki; Chauhan, Sunil K.; Dana, Reza.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 1, 01.01.2013, p. 813-820.

Research output: Contribution to journalArticle

Ferrari, Giulio ; Hajrasouliha, Amir R. ; Sadrai, Zahra ; Ueno, Hiroki ; Chauhan, Sunil K. ; Dana, Reza. / Nerves and neovessels inhibit each other in the cornea. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 1. pp. 813-820.
@article{9ece3cc9d7054c938dc0c8e5dd74b889,
title = "Nerves and neovessels inhibit each other in the cornea",
abstract = "PURPOSE. To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea. METHODS. b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epitheliumderived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining. RESULTS. No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5{\%} reduction, P = 0.001) and PEDF protein expression (64{\%} reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed. CONCLUSION. Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis.",
author = "Giulio Ferrari and Hajrasouliha, {Amir R.} and Zahra Sadrai and Hiroki Ueno and Chauhan, {Sunil K.} and Reza Dana",
year = "2013",
month = "1",
day = "1",
doi = "10.1167/iovs.11-8379",
language = "English (US)",
volume = "54",
pages = "813--820",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "1",

}

TY - JOUR

T1 - Nerves and neovessels inhibit each other in the cornea

AU - Ferrari, Giulio

AU - Hajrasouliha, Amir R.

AU - Sadrai, Zahra

AU - Ueno, Hiroki

AU - Chauhan, Sunil K.

AU - Dana, Reza

PY - 2013/1/1

Y1 - 2013/1/1

N2 - PURPOSE. To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea. METHODS. b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epitheliumderived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining. RESULTS. No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5% reduction, P = 0.001) and PEDF protein expression (64% reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed. CONCLUSION. Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis.

AB - PURPOSE. To evaluate the regulatory cross-talk of the vascular and neural networks in the cornea. METHODS. b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day 7, blood vessels (hemangiogenesis) and nerves were observed by immunofluorescence staining of corneal flat mounts. The next group of mice underwent either trigeminal stereotactic electrolysis (TSE), or sham operation, to ablate the ophthalmic branch of the trigeminal nerve. Blood vessel growth was detected by immunohistochemistry for PECAM-1 (CD31) following surgery. In another set of mice following TSE or sham operation, corneas were harvested for ELISA (VEGFR3 and pigment epitheliumderived factor [PEDF]) and for quantitative RT-PCR (VEGFR3, PEDF, and CD45). PEDF, VEGFR3, beta-3 tubulin, CD45, CD11b, and F4/80 expression in the cornea were evaluated using immunostaining. RESULTS. No nerves were detected in the areas subject to corneal neovascularization, whereas they persisted in the areas that were neovessel-free. Conversely, 7 days after denervation, significant angiogenesis was detected in the cornea, and this was associated with a significant decrease in VEGFR3 (57.5% reduction, P = 0.001) and PEDF protein expression (64% reduction, P < 0.001). Immunostaining also showed reduced expression of VEGFR3 in the corneal epithelial layer. Finally, an inflammatory cell infiltrate, including macrophages, was observed. CONCLUSION. Our data suggest that sensory nerves and neovessels inhibit each other in the cornea. When vessel growth is stimulated, nerves disappear and, conversely, denervation induces angiogenesis. This phenomenon, here described in the eye, may have far-reaching implications in understanding angiogenesis.

UR - http://www.scopus.com/inward/record.url?scp=84874720799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874720799&partnerID=8YFLogxK

U2 - 10.1167/iovs.11-8379

DO - 10.1167/iovs.11-8379

M3 - Article

VL - 54

SP - 813

EP - 820

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 1

ER -