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It's a mouse study, and the protein acronym babble is always way over my head, but the basic concept I've never come across before. And...
RESULTS: No nerves were detected in the areas subject to corneal neovascularization,
Nerves and Neovessels Inhibit Each Other in the Cornea.
PURPOSE:
to evaluate the regulatory cross talk of the vascular and neural networks in the cornea.
Methods:
b-FGF micropellets (80ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day seven, 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 Epithelium Derived 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, while they persisted in the areas that were neovessel-free. Conversely, seven 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 and PEDF expression in the normal 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.
to evaluate the regulatory cross talk of the vascular and neural networks in the cornea.
Methods:
b-FGF micropellets (80ng) were implanted in the temporal side of the cornea of healthy C57Bl/6 mice. On day seven, 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 Epithelium Derived 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, while they persisted in the areas that were neovessel-free. Conversely, seven 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 and PEDF expression in the normal 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.
Ferrari G, Hajrasouliha AR, Sadrai ZP, Ueno H, Chauhan SK, Dana R.
Ophthalmology - Cornea and Ocular Surface Unit - Eye Repair, San Raffaele Scientific Institute, Via Olgettina, 60, Milan, Italy.