B-FGF Induces Corneal Blood and Lymphatic Vessel Growth in a Spatially Distinct Pattern

Overview

Journal Cornea

Specialty Ophthalmology

Date 2012 Apr 3

PMID 22467003

Citations 10

Authors

Amir R Hajrasouliha

Zahra Sadrai

Sunil K Chauhan

Reza Dana

Affiliations

Soon will be listed here.

Abstract

Purpose: To study the spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by basic fibroblast growth factor (b-FGF).

Methods: b-FGF micropellets (80 ng) were implanted in the temporal side of the cornea of Balb/c mice. On days 1, 3, and 7, blood (heme-) and lymphangiogenesis were observed by immunofluorescence staining of corneal flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels, respectively. A second group of corneas were harvested for quantitative real-time polymerase chain reaction. Each cornea was divided into 2 different areas: (1) pre-pellet area and (2) opposite-pellet area. Expression of vascular endothelial growth factor (VEGF) ligands was evaluated using real-time polymerase chain reaction in each respective zone.

Results: Blood vessels grew into the cornea from the pre-pellet area, whereas corneal lymphatic vessels grew from the opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in the pre-pellet, whereas VEGF-D expression was mostly observed in the opposite-pellet area. VEGF-C level increased simultaneously in both areas.

Conclusions: A single inducing factor, that is, b-FGF, may simultaneously provoke hemangiogenesis and lymphangiogenesis in different locations of the cornea through differential expression of VEGF ligands. This distinctive spatial pattern should be considered while evaluating the corneal predilection for inflammation beyond that which is directly visible by slit lamp examination.

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References

Tammela T, Saaristo A, Lohela M, Morisada T, Tornberg J, Norrmen C . Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Blood. 2005; 105(12):4642-8. DOI: 10.1182/blood-2004-08-3327. View

Alitalo K, Carmeliet P . Molecular mechanisms of lymphangiogenesis in health and disease. Cancer Cell. 2002; 1(3):219-27. DOI: 10.1016/s1535-6108(02)00051-x. View

Bock F, Onderka J, Dietrich T, Bachmann B, Pytowski B, Cursiefen C . Blockade of VEGFR3-signalling specifically inhibits lymphangiogenesis in inflammatory corneal neovascularisation. Graefes Arch Clin Exp Ophthalmol. 2007; 246(1):115-9. DOI: 10.1007/s00417-007-0683-5. View

Cursiefen C . Immune privilege and angiogenic privilege of the cornea. Chem Immunol Allergy. 2007; 92:50-57. DOI: 10.1159/000099253. View

Thurston G . Role of Angiopoietins and Tie receptor tyrosine kinases in angiogenesis and lymphangiogenesis. Cell Tissue Res. 2003; 314(1):61-8. DOI: 10.1007/s00441-003-0749-6. View

Hill J . High risk corneal grafting. Br J Ophthalmol. 2002; 86(9):945. PMC: 1771275. DOI: 10.1136/bjo.86.9.945. View

Dietrich T, Onderka J, Bock F, Kruse F, Vossmeyer D, Stragies R . Inhibition of inflammatory lymphangiogenesis by integrin alpha5 blockade. Am J Pathol. 2007; 171(1):361-72. PMC: 1941598. DOI: 10.2353/ajpath.2007.060896. View

Chung E, Saban D, Chauhan S, Dana R . Regulation of blood vessel versus lymphatic vessel growth in the cornea. Invest Ophthalmol Vis Sci. 2008; 50(4):1613-8. PMC: 2702143. DOI: 10.1167/iovs.08-2212. View

Ferrara N . The biology of vascular endothelial growth factor. Endocr Rev. 1997; 18(1):4-25. DOI: 10.1210/edrv.18.1.0287. View

10.

Cao Y, Zhong W . Tumor-derived lymphangiogenic factors and lymphatic metastasis. Biomed Pharmacother. 2007; 61(9):534-9. DOI: 10.1016/j.biopha.2007.08.009. View

11.

Slavin J . Fibroblast growth factors: at the heart of angiogenesis. Cell Biol Int. 1995; 19(5):431-44. DOI: 10.1006/cbir.1995.1087. View

12.

Morisada T, Oike Y, Yamada Y, Urano T, Akao M, Kubota Y . Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation. Blood. 2005; 105(12):4649-56. DOI: 10.1182/blood-2004-08-3382. View

13.

Eswarakumar V, Lax I, Schlessinger J . Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005; 16(2):139-49. DOI: 10.1016/j.cytogfr.2005.01.001. View

14.

Cao R, Bjorndahl M, Religa P, Clasper S, Garvin S, Galter D . PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell. 2004; 6(4):333-45. DOI: 10.1016/j.ccr.2004.08.034. View

15.

Dana M . Angiogenesis and lymphangiogenesis-implications for corneal immunity. Semin Ophthalmol. 2006; 21(1):19-22. DOI: 10.1080/08820530500509358. View

16.

Rossant J, Hirashima M . Vascular development and patterning: making the right choices. Curr Opin Genet Dev. 2003; 13(4):408-12. DOI: 10.1016/s0959-437x(03)00080-7. View

17.

Ortega S, Ittmann M, Tsang S, Ehrlich M, Basilico C . Neuronal defects and delayed wound healing in mice lacking fibroblast growth factor 2. Proc Natl Acad Sci U S A. 1998; 95(10):5672-7. PMC: 20437. DOI: 10.1073/pnas.95.10.5672. View

18.

Magnusson P, Rolny C, Jakobsson L, Wikner C, Wu Y, Hicklin D . Deregulation of Flk-1/vascular endothelial growth factor receptor-2 in fibroblast growth factor receptor-1-deficient vascular stem cell development. J Cell Sci. 2004; 117(Pt 8):1513-23. DOI: 10.1242/jcs.00999. View

19.

Itoh N . The Fgf families in humans, mice, and zebrafish: their evolutional processes and roles in development, metabolism, and disease. Biol Pharm Bull. 2007; 30(10):1819-25. DOI: 10.1248/bpb.30.1819. View

20.

Chen L, Hamrah P, Cursiefen C, Zhang Q, Pytowski B, Wayne Streilein J . Vascular endothelial growth factor receptor-3 mediates induction of corneal alloimmunity. Nat Med. 2004; 10(8):813-5. DOI: 10.1038/nm1078. View