Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits

Journal of Clinical Investigation

Volumn 118, Issue 6, 2008, Pages 2337-2346

  Scheppke, Lea ^a   Aguilar, Edith ^a   Gariano, Ray F ^a   Jacobson, Ruth ^a   Hood, John ^b   Doukas, John ^b   Cao, Jon ^b   Noronha, Glenn ^b   Yee, Shiyin ^b   Weis, Sara ^c   Martin, Michael B ^b   Soll, Richard ^b   Cheresh, David A ^c   Friedlander, Martin ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b TargeGen Inc   (United States)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO 7 TERT BUTYL 5 (4 METHYLPHENYL)PYRAZOLO[3,4 D]PYRIMIDINE; BOSUTINIB; PROTEIN TYROSINE KINASE; TG 100572; VASCULOTROPIN; VASCULOTROPIN INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD VESSEL PERMEABILITY; CONTROLLED STUDY; GENETIC ANALYSIS; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RABBIT; RETINA BLOOD VESSEL;

ANIMALS; CAPILLARY PERMEABILITY; ENZYME INHIBITORS; MICE; MICE, INBRED BALB C; MICE, TRANSGENIC; MODELS, BIOLOGICAL; PERMEABILITY; RABBITS; RETINA; SIGNAL TRANSDUCTION; SRC-FAMILY KINASES; TIME FACTORS; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 45749143528     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI33361     Document Type: Article

References (50)

1. Cunha-Vaz, J.G. 1983. Studies on the pathophysiology of diabetic retinopathy. The blood-retinal barrier in diabetes. Diabetes. 32(Suppl. 2):20-27.
2. Chahal, P.S., Fallon, T.J., and Kohner, E.M. 1986. Measurement of blood-retinal barrier function in central retinal vein occlusion. Arch. Ophthalmol. 104:554-557.
3. Caldwell, R.B., et al. 2003. Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab. Res. Rev. 19:442-455.
4. Boyd, S.R., et al. 2002. Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch. Ophthalmol. 120:1644-1650.
5. Qaum, T., et al. 2001. VEGF-initiated blood-retinal barrier breakdown in early diabetes. Invest. Ophthalmol. Vis. Sci. 42:2408-2413.
6. Antonetti, D.A., et al. 1998. Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes. 47:1953-1959.
7. Vinores, S.A., et al. 1997. Upregulation of vascular endothelial growth factor in ischemic and nonischemic human and experimental retinal disease. Histol. Histopathol. 12:99-109.
8. Fine, H.F., Baffi, J., Reed, G.F., Csaky, K.G., and Nussenblatt, R.B. 2001. Aqueous humor and plasma vascular endothelial growth factor in uveitis-associated cystoid macular edema. Am. J. Ophthalmol. 132:794-796.
9. Rosenfeld, P.J., et al. 2006. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 355:1419-1431.
10. Eliceiri, B.P., et al. 1999. Selective requirement for SRC kinases during VEGF-induced angiogenesis and vascular permeability. Mol. Cell. 4:915-924.
11. Yuan, S.Y. 2002. Protein kinase signaling in the modulation of microvascular permeability. Vascul. Pharmacol. 39:213-223.
12. Paul, R., et al. 2001. SRC deficiency or blockade of SRC activity in mice provides cerebral protection following stroke. Nat. Med. 7:222-227.
13. Weis, S., et al. 2004. SRC blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction. J. Clin. Invest. 113:885-894.
14. Owens, D.W., et al. 2000. The catalytic activity of the SRC family kinases is required to disrupt cadherin-dependent cell-cell contacts. Mol. Biol. Cell. 11:51-64.
15. Kevil, C.G., Payne, D.K., Mire, E., and Alexander, J.S. 1998. Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins. J. Biol. Chem. 273:15099-15103.
16. Weis, S.M., and Cheresh, D.A. 2005. Pathophysiological consequences of VEGF-induced vascular permeability. Nature. 437:497-504.
17. Chou, M.T., Wang, J., and Fujita, D.J. 2002. SRC kinase becomes preferentially associated with the VEGFR, KDR/Flk-1, following VEGF stimulation of vascular endothelial cells. BMC Biochem. 3:32.
18. Weis, S., Cui, J., Barnes, L., and Cheresh, D. 2004. Endothelial barrier disruption by VEGF-mediated SRC activity potentiates tumor cell extravasation and metastasis. J. Cell Biol. 167:223-229.
19. Boschelli, D.H., et al. 2001. Optimization of 4-phenylamino-3- quinolinecarbonitriles as potent inhibitors of SRC kinase activity. J. Med. Chem. 44:3965-3977.
20. Blake, R.A., et al. 2000. SU6656, a selective SRC family kinase inhibitor, used to probe growth factor signaling. Mol. Cell. Biol. 20:9018-9027.
21. Golas, J.M., et al. 2003. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of SRC and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 63:375-381.
22. Nunes, I., Higgins, R.D., Zanetta, L., Shamamian, P., and Goff, S.P. 2001. c-abl is required for the development of hyperoxia-induced retinopathy. J. Exp. Med. 193:1383-1391.
23. Werdich, X.Q., and Penn, J.S. 2006. Specific involvement of SRC family kinase activation in the pathogenesis of retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 47:5047-5056.
24. Noronha, G., et al. 2007. Discovery of [7- (2,6-dichlorophenyl)-5- methylbenzo [1,2,4]triazin-3-yl]-[4- (2-pyrrolidin-1-ylethoxy)phenyl]amine - a potent, orally active SRC kinase inhibitor with anti-tumor activity in preclinical assays. Bioorg. Med. Chem. Lett. 17:602-608.
25. Ciulla, T.A., Amador, A.G., and Zinman, B. 2003. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 26:2653-2664.
26. Ferris, F. 1996. Early photocoagulation in patients with either type I or type II diabetes. Trans. Am. Ophthalmol. Soc. 94:505-537.
27. Avery, R.L., et al. 2006. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology. 113:363-372e5.
28. Ferrara, N., Gerber, H.P., and LeCouter, J. 2003. The biology of VEGF and its receptors. Nat. Med. 9:669-676.
29. Alon, T., et al. 1995. Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat. Med. 1:1024-1028.
30. Storkebaum, E., Lambrechts, D., and Carmeliet, P. 2004. VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. Bioessays. 26:943-954.
31. Bates, D.O., and Harper, S.J. 2002. Regulation of vascular permeability by vascular endothelial growth factors. Vascul. Pharmacol. 39:225-237.
32. Tolentino, M.J., et al. 2002. Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate. Am. J. Ophthalmol. 133:373-385.
33. Frank, R.N. 2004. Diabetic retinopathy. N. Engl. J. Med. 350:48-58.
34. Mathews, M.K., Merges, C., McLeod, D.S., and Lutty, G.A. 1997. Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 38:2729-2741.
35. Lowell, C.A., and Soriano, P. 1996. Knockouts of SRC-family kinases: stiff bones, wimpy T cells, and bad memories. Genes Dev. 10:1845-1857.
36. Tinsley, J.H., Ustinova, E.E., Xu, W., and Yuan, S.Y. 2002. SRC-dependent, neutrophil-mediated vascular hyperpermeability and beta-catenin modification. Am. J. Physiol. Cell Physiol. 283:C1745-C1751.
37. Eliceiri, B.P., et al. 2002. SRC-mediated coupling of focal adhesion kinase to integrin alpha (v)beta5 in vascular endothelial growth factor signaling. J. Cell Biol. 157:149-160.
38. Birukov, K.G., et al. 2001. Differential regulation of alternatively spliced endothelial cell myosin light chain kinase isoforms by p60 (SRC). J. Biol. Chem. 276:8567-8573.
39. Hofman, P., et al. 2000. VEGF-A induced hyperpermeability of blood-retinal barrier endothelium in vivo is predominantly associated with pinocytotic vesicular transport and not with formation of fenestrations. Vascular endothelial growth factor-A. Curr. Eye Res. 21:637-645.
40. Sanguinetti, A.R., Cao, H., and Corley Mastick, C. 2003. Fyn is required for oxidative- and hyperosmotic-stress-induced tyrosine phosphorylation of caveolin-1. Biochem. J. 376:159-168.
41. Dorrell, M.I., Aguilar, E., Scheppke, L., Barnett, F.H., and Friedlander, M. 2007. Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. Proc. Natl. Acad. Sci. U. S. A. 104:967-972.
42. Rogers, M.S., and D'Amato, R.J. 2006. The effect of genetic diversity on angiogenesis. Exp. Cell Res. 312:561-574.
43. Lindbom, L. 2003. Regulation of vascular permeability by neutrophils in acute inflammation. Chem. Immunol. Allergy. 83:146-166.
44. Xu, Q., Qaum, T., and Adamis, A.P. 2001. Sensitive blood-retinal barrier breakdown quantitation using Evans blue. Invest. Ophthalmol. Vis. Sci. 42:789-794.
45. He, H., et al. 1999. Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-SRC. J. Biol. Chem. 274:25130-25135.
46. Watzke, R.C., et al. 2000. A comparison of stereoscopic fluorescein angiography with indocyanine green videoangiography in age-related macular degeneration. Ophthalmology. 107:1601-1606.
47. Dorrell, M.I., Aguilar, E., and Friedlander, M. 2002. Retinal vascular development is mediated by endothelial filopodia, a preexisting astrocytic template and specific R-cadherin adhesion. Invest. Ophthalmol. Vis. Sci. 43:3500-3510.
48. Derevjanik, N.L., et al. 2002. Quantitative assessment of the integrity of the blood-retinal barrier in mice. Invest. Ophthalmol. Vis. Sci. 43:2462-2467.
49. Miller, J.W., et al. 1994. Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am. J. Pathol. 145:574-584.
50. Stein, P.L., Vogel, H., and Soriano, P. 1994. Combined deficiencies of SRC, Fyn, and Yes tyrosine kinases in mutant mice. Genes Dev. 8:1999-2007.