ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Ж-л "Biotechnologia Acta" Т. 14, № 1 , 2021
С. 5-24, библиогр. 110, англ.
УДК: 577.112.5: 57.088
https://doi.org/10.15407/biotech14.01.005
Full text: (PDF, in English)
PRODUCTION AND APPLICATION OF ANGIOSTATINS FOR THE TREATMENT OF OCULAR NEOVASCULAR DISEASES
Bilous V. L., Kapustianenko L. G., Tykhomyrov A. A.
Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv
Angiostatins comprise a group of kringle-containing proteolytically-derived plasminogen/plasmin fragments, which act as potent inhibitory mediators of endothelial sells proliferation and migration. Angiostatins are involved in modulation of vessel growth in healthy tissues and various pathological conditions associated with aberrant neovascularization. The aim of the present paper was to summarize available information, including our own experimental data, on prospects of angiostatin application for treatment of ocular neovascular diseases (OND), focusing on retinal pathologies and corneal injury. In particular, literature data on prospective and retrospective studies, clinical trials and animal models relating to the pathophysiology, investigation and management of OND are described. Special emphasis was made on the laboratory approaches of production of different angiostatin isoforms, as well as comparison of antiangiogenic capacities of native and recombinant angiostatin polypeptides. Several studies reported that angiostatins may completely abolish pathologic angiogenesis in diabetic proliferative retinopathy without affecting normal retinal vessel development and without exhibiting adverse side effects. Angiostatins have been tested as a tool for corneal antiangiogenesis target therapy in order to manage diverse ocular surface pathological conditions induced by traumas, chemical burns, previous surgery, chronic contact lens wear, autoimmune diseases, keratitis and viral infections (herpes, COVID-19), corneal graft rejection, etc. Among all known angiostatin species, isolated K5 plasminogen fragment was shown to display the most potent inhibitory activity against proliferation of endothelial cells via triggering multiple signaling pathways, which lead to cell death and resulting angiogenesis suppression. Application of adenoviral genetic construct encoding angiostatin K5 as a promising tool for OND treatment illustrates a vivid example of upcoming revolution in local gene therapy. Further comprehensive studies are necessary to elucidate the clinical potential and optimal regimes of angiostatin-based intervention modalities for treating ocular neovascularization.
Key words: angiostatins, ocular neovascular diseases, retinopathy, corneal neovascularization, antiangiogenic therapy, local gene delivery.
© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2021
References
1. Flaxman S. R., Bourne R. R. A., Resnikoff S., Ackland P. et al. Vision Loss Expert Group of the Global Burden of Disease Study. Global causes of blindness and distance vision impairment 1990-2020: a systematic review and meta-analysis. Lancet Glob. Health. 2017, 5 (12), e122–e1234. https://doi.org/10.1016/ S2214-109X(17)30393-5
2. Lin F.-L., W ang P.-Y., Chua ng Y.-F., Wang J.-H., Wong V. H. Y., Bui B. V., Liu G.-Sh. Gene therapy intervention in neovascular eye disease: a recent update. Molecular Therapy. 2020, 28 (10), 2120–2138. https://doi.org/10.1016/j.ymthe.2020.06.029
3. Cabral T., Mello L. G. M., Lima L. H., Polido J., Regatieri C. V., Belfort R. Jr., Mahajan V. B. Retinal and choroidal angiogenesis: a review of new targets. Int. J. Retina Vitreous. 2017, V. 3, P. 31. https://doi.org/10.1186/s40942-017-0084-9
4. Friedlander M. Fibrosis and diseases of the eye. J. Clin. Invest. 2007, 117 (3), 576–586. https://doi.org/10.1172/JCI31030
S., Dorrell M. I., Scheppke L., Bucher F., Sakimoto S., Paris L. P., Aguilar E., Friedlander M. Angiogenesis and eye disease. Annu Rev. Vis. Sci. 2015, V. 1, P. 155–184. https://doi.org/10.1146/annurev-vision-082114-035439
6. Ma Q., Reiter R. J., Chen Y. Role of melatonin in controlling angiogenesis under physiological and pathological conditions. Angiogenesis. 2020, 23 (2), 91–104. https://doi.org/10.1007/s10456-019-09689-7
7. Xi L. Pigment epithelium-derived factor as a possible treatment agent for choroidal neovascularization. Oxid. Med. Cell. Longev. 2020, V. 2020, P. 8941057. https://doi.org/10.1155/2020/8941057
8. Di Somma M., Vliora M., Grillo E., Castro B. Dakou E., Schaafsma W.,·Vanparijs J., CorsiniM.,·Ravelli C.,·Sakellariou E.,·Mitola S. Role of VEGFs in metabolic disorders. Angiogenesis. 2020, 23 (2), 119–130. https://doi.org/10.1007/s10456-019-09700-1
9. Hu Y., Tang S. Major challenges in vitreoretinal surgery. Taiwan J. Ophthalmol. 2015, 5 (1), 9–14. https://doi.org/10.1016/j.tjo.2014.04.005
10. Andreoli C. M., Miller J. W. Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr. Opin. Ophthalmol. 2007, 18 (6), 502–508. https://doi.org/10.1097/ICU.0b013e3282f0ca54
11. O’Reilly M. S., Boehm T., Shing Y., Fukai N., Vasios G., Lane W. S., Flynn E., Birkhead J. R., Olsen B. R., Folkman J. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997, V. 88, P.277– 285. https://doi.org/10.1016/S0092-8674(00)81848-6
12. Cao Y., Ji R., Davidson D., Schaller J., Marti D., Sohndel S., McCance S., O’Reilly M., Llinas M., Folkman J. Kringle domains of human angiostatin. Characterization of the anti-proliferative activity on endothelial cells. J. Biol. Chem. 1996, V. 271, P. 29461–29467. https://doi.org/10.1074/jbc.271.46.29461
13. Castellino F. J., McCance S. G. The kringle domains of human plasminogen. Ciba Found. Symp. 1997, V. 212, P. 46–60. https://doi.org/10.1002/9780470515457.ch4
14. Cao Y., Chen A., An S. S. A., Ji R.-W., David sonD., Cao Y., Llinas M. Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth. J. Biol. Chem. 1997, V. 272, P. 22924–22928. https://doi.org/10.1074/jbc.272.36.22924
15. Lu H., Dhanabal M., Volk R., Waterman M. J., Ramchandran R., Knebelmann B., Segal M., Sukhatme V. P. Kringle 5 causes cell cycle arrest and apoptosis of endothelial cells. Biochem. Biophys. Res. Commun. 1999, V. 258, P. 668–673. https://doi.org/10.1006/bbrc.1999.0612
16. Ji W. R., Barrientos L. G., Llinas M., Gray H., Villarreal X., DeFord M. E., Castellino F. J., Kramer R. A., Trail P. A. Selective inhibition by kringle 5 of human plasminogen on endothelial cell migration, an important process in angiogenesis. Biochem. Biophys. Res. Commun. 1998, V. 247, P. 414–419. https://doi.org/10.1006/bbrc.1998.8825
17. Kapustianenko L. G., Iatsenko T. A., Yusova E. I., Grinenko T. V. Isolation and purification of a kringle 5 from human plasminogen using AH-Sepharose. Biotechnol. acta. 2014, 7 (4), 35–42. https://doi.org/10.15407/biotech7.04.035
18. Tykhomyrov A. A., Yusova E. I., Diordieva S. I., Corsa V. V., Grinenko T. V. Production and characteristics of antibodies against K1-3 fragment of human plasminogen. Biotechnol. acta. 2013, 6 (1), 86–96. (In Ukrainian). https://doi.org/10.15407/biotech6.01.086
19. Kapustianenko L. G. Polyclonal antibodies against human plasminogen kringle 5. Biotechnol. acta. 2017, 10 (3), 41–49. https://doi.org/10.15407/biotech10.03.041
20. Roka-Moya Y. M., Zhernossekov D. D., Yu sova E. I., Kapustianenko L. G., Grinen ko T. V. Study of the sites of plasminogen molecule which are responsible for inhibitory effect of Lys-plasminogen on platelet aggregation. Ukr. Biochem. J. 2014, 86 (5), 82–88. https://doi.org/10.15407/ubj86.05.082
21. Niu G., Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr. Drug. Targets. 2010, 11 (8), 1000–1017. https://doi.org/10.2174/138945010791591395
22. Feizi S., Azari A. A., Safapour S. Therapeutic approaches for corneal neovascularization. Eye Vis. 2017, 4 (28), 1–10. https://doi.org/10.1186/s40662-017-0094-6
23. Coats D. K. Retinopathy of prematurity: involution, factors predisposing to retinal detachment, and expected utility of preemptive surgical reintervention. Trans. Am. Ophthalmol. Soc. 2005, V. 103, P. 281– 312. PMID: 17057808
24. Campbell M., Humphries P. The bloodretina barrier: tight junctions and barrier modulation. Adv. Exp. Med. Biol. 2012, V. 763, P. 70–84. PMID: 23397619, https://doi.org/10.1007/978-1-4614-4711-5_3
25. Cunha-Vaz J., Bernardes R., Lobo C. Bloodretinal barrier. Eur. J. Ophthalmol. 2011, 21 (6), 3–9. https://doi.org/10.5301/EJO.2010.6049
26. O’Connor A. R., Wilson C. M., Fielder A. R. Ophthalmological problems associated with preterm birth. Eye (Lond.). 2007, 21 (10), 1254–1260. https://doi.org/10.1038/sj.eye.6702838
27. Sun J. K., Radwan S. H., Soliman A. Z., Lammer J., Lin M. M., Prager S. G., Silva P. S., Aiello L. B., Aiello L. P. Neural Retinal Disorganization as a Robust Marker of Visual Acuity in Current and Resolved Diabetic Macular Edema. Diabetes. 2015, 64 (7), 2560–2570. https://doi.org/10.2337/db14-0782
28. Campochiaro P. Ocular Neovascularization. J. Mol. Med. (Berl.) 2013, 91 (3), 311–321. https://doi.org/10.1007/s00109-013-0993-5
29. GBD 2019 Blindness and Vision Impairment Collaborators on behalf of the Vision Loss; Expert Group of the Global Burden of Disease Study. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study. Lancet Global Health. 2020. S2214- 109X(20)30489-7. https://doi.org/10.1016/ S2214-109X(20)30489-7
30. Gadzhieva B. K. Ocular neovascular-related diseases: immunological mechanisms of development and the potential of antiangiogenic therapy. Ophthalmol. J. 2016, 9 (4), 58–67. https://doi.org/10.17816/OV9458-67
31. Beebe D. C. Maintaining transparency: a review of the developmental physiology and pathophysiology of two avascular tissues. Semin. Cell. Dev. Biol. 2008, 19 (2), 125–133. https://doi.org/10.1016/j.semcdb.2007.08.014
32. Chang J. H., Gabison E. E., Kato T., Azar D. T. Corneal neovascularization. Curr. Opin. Ophthalmol. 2001, 12 (4), 242–249. https://doi.org/10.1097/00055735-200108000-00002
33. Lee P., Wang C. C., Adamis A. P. Ocular neovascularization: an epidemiologic review. Surv. Ophthalmol. 1998, 43 (3), 245–269. https://doi.org/10.1016/S0039-6257(98)00035-6
34. Abdelfattah N. S., Amgad M., Zayed A. A., Salem H., Elkhanany A. E., Hussein H., Abd El-Baky N. Clinical correlates of common corneal neovascular diseases: A literature review. Int. J. Ophthalmol. 2015, 8 (1), 182– 193. https://doi.org/10.3980/j.issn.2222- 3959.2015.01.32
35. Sharif Z., Sharif W. C o r n e a l neovascularization: updates on pathophysiology, investigations & management. Rom. J. Ophthalmol. 2019, 63 (1), 15–22. https://doi.org/10.22336/rjo.2019.4
36. Pons-Cursach R., Casanovas O. Mechanisms of Anti-Angiogenic Therapy. Tumor Angiogenesis. 2017, P. 1–25. https://doi.org/10.1007/978-3-319-31215-6_2-2
37. Roodhart J. M., Langenberg M. H., Witteveen E., Voest E. E. The molecular basis of class side effects due to treatment with inhibitors of the VEGF/VEGFR pathway. Curr. Clin. Pharmacol. 2008, 3 (2), 132–143. https://doi.org/10.2174/157488408784293705
38. Griffioen A. W., Molema G. Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol. Rev. 2000, 52 (2), 237–268. PMID: 10835101
39. Polverini P. J. Angiogenesis in health and disease: insights into basic mechanisms and therapeutic opportunities. J. Dent. Educ. 2002, 66 (8), 962–975. PMID: 12214844, https://doi.org/10.1002/j.0022-0337.2002.66.8.tb03565.x
40. Yang H., Yu X., Sun X. Neovascular glaucoma: handling in the future. Taiwan J. Ophthalmol. 2018, 8 (2), 60–66. https://doi.org/10.4103/tjo.tjo_39_18
41. O’Reilly M. S., Holmgren L., Shing Y., Chen C., Rosenthal R. A., Moses M., Lane W. S., Cao Y., Sage E. H., Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994, V. 79, P. 315–328. https://doi.org/10.1016/0092-8674(94)90200-3
42. Lee T. Y., Muschal S., Pravda E. A., Folkman J., Abdollahi A., Javaherian K. Angiostatin regulates the expression of antiangiogenic and proapoptotic pathways via targeted inhibition of mitochondrial proteins. Blood. 2009, 114 (9), 1987–1998. https://doi.org/10.1182/blood-2008-12-197236
43. Cao R., Wu H. L., Veitonm?ki N., Linden P., Farnebo J., Shi G. Y., Cao Y. Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasminmediated proteolysis. Proc. Natl. Acad. Sci. USA. 1999, 96 (10), 5728–5733. https://doi.org/10.1073/pnas.96.10.5728
44. Cao Y., Chen A., An S. S., Ji R. W., Davidson D., Llin?s M. Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth. J. Biol. Chem. 1997, 272 (36), 22924–22928. https://doi.org/10.1074/jbc.272.36.22924
45. Gonzalez-Gronow M., Kalfa T., Johnson C. E., Gawdi G., Pizzo S. V. The voltage-dependent anion channel is a receptor for plasminogen kringle 5 on human endothelial cells. J. Biol. Chem. 2003, 278 (29), 27312–27318. https://doi.org/10.1074/jbc.M303172200
46. Tarui T., Mazar A. P., Cines D. B., Takada Y. Urokinase-type plasminogen activator receptor (CD87) is a ligand for integrins and mediates cell-cell interaction. J. Biol. Chem. 2001, V. 276, P. 3983–3990. https://doi.org/10.1074/jbc.M008220200
47. Bohnsack R. N., Patel M., Olson L. J., Twining S. S., Dahms N. M. Residues essential for plasminogen binding by the cation-independent mannose 6-phosphate receptor. Biochem. 2010, 49 (3), 635–644. https://doi.org/10.1021/bi901779p
48. Llombart-Bosch A., L?pez-Guerrero J. A., Felipo V. New trends in cancer for the 21st century. Springer Netherlands. 2006, P. 251–275. https://doi.org/10.1007/978-1-4020-5133-3
49. Cao Y., Xue L. Angiostatin. Semin. Thromb. Hemost. 2004, 30 (1), 83–93. https://doi.org/10.1055/s-2004-822973
50. B?hm M. R., Hodes F., Brockhaus K., Hummel S., Schlatt S., Melkonyan H., Thanos S. Is angiostatin involved in physiological foveal avascularity? Invest. Ophthalmol. Vis. Sci. 2016, 57 (11), 4536–4552. https://doi.org/10.1167/iovs.16-19286
51. Tykhomyrov A. A., Shram S. I., Grinenko T. V. The Role of angiostatins in diabetic complications. Biochemistry (Moscow). Supplement Series B. Biomedical Chemistry. 2014, 8 (2), 94–107 https://doi.org/10.1134/S1990750814020140
52. Spranger J., B?hnen J., Jansen V. Systemic levels contribute significantly to increased intraocular IGF-I, IGF-II and IGF-BP3 [correction of IFG-BP3] in proliferative diabetic retinopathy. Horm. Metab. Res. 2000, 32 (5), 196–200. https://doi.org/10.1055/s-2007-978621
53. Guzyk M. M., Tykhomyrov A. A., Nedzvetsky V. S., Prischepa I. V., Grinenko T. V., Yanitska L. V., Kuchmerovska T. M. Poly(ADP-Ribose) polymerase-1 (PARP-1) inhibitors reduce reactive gliosis and improve angiostatin levels in retina of diabetic rats. Neurochem. Res. 2016, 41 (10), 2526–2537. https://doi.org/10.1007/s11064-016-1964-3
54. Lai С. С., Wu W. C., Chen S. L. Suppression of choroidal neovascularization by adeno-associated virus vector expressing angiostatin. Vis. Sci. 2001, 42 (10), 2401– 2407.
55. Liguori I., Russo G., Curcio F., Bulli G., Aran L., Della-Morte D., Gargiulo G., Testa G., Cacciatore F., Bonaduce D., Abete P. Oxidative stress, aging, and diseases. Clin. Interv. Aging. 2018, V. 13, P. 757–772. https://doi.org/10.2147/CIA.S158513
56. Ali M. M., Janic B., Babajani-Feremi A., Varma N. R., Iskander A. S., Anagli J., Arbab A. S. Changes in vascular permeability and expression of different angiogenic factors following anti-angiogenic treatment in rat glioma. PLoS One. 2010, 5 (1), e8727. https://doi.org/10.1371/journal.pone.0008727
57. Penn J. S., Madan A., Caldwell R. B., Bartoli M., Caldwell R. W., Hartnett M. E. Vascular endothelial growth factor in eye disease. Prog. Retin. Eye Res. 2008, 27 (4), 331–371. https://doi.org/10.1016/j.preteyeres.2008.05.001
58. Fitzgerald K. A., O’Neill L. A. J., Gearing A. J. H., Callard R. E. Angiostatin. The Cytokine Facts Book and Webfacts (Second Edition), Academic Press. 2001, P. 139–141. https://doi.org/10.1016/B978-012155142-1/50026-9
59. Sima J., Zhang S. X., Shao C. The effect of angiostatin on vascular leakage and VEGF expression in rat retina. FEBS Letters. 2004, 564 (1–2), 19–23. https://doi.org/10.1016/S0014-5793(04)00297-2
60. Macsai M., Mojica G. Ocular surface disease: cornea, conjunctiva and tear film. Saunders. 2013, P. 293–308. https://doi.org/10.1016/B978-1-4557-2876-3.00036-5
61. Klopfer J., Tielsch J. M., Vitale S., See L. C., Canner J. K. Ocular trauma in the United States. Eye injuries resulting in hospitalization, 1984 through 1987. Arch. Ophthalmol. 1992, 110 (6), 838–842. https://doi.org/10.1001/archopht.1992.01080180110037
62. Thylefors B. Epidemiological patterns of ocular trauma. Aust N. Z. J. Ophthalmol. 1992, 20 (2), 95–98. https://doi.org/10.1111/j.1442-9071.1992.tb00718.x
63. Lim C. H., Turner A., Lim B. X. Patching for corneal abrasion. Cochrane Database Syst. Rev. 2016, 7 (7), CD004764. https://doi.org/10.1002/14651858.CD004764.pub3
64. Hossain R. R., Papamichael E., Coombes A. East London deliberate corrosive fluid injuries. Eye (Lond). 2020, 34 (4), 733–739. https://doi.org/10.1038/s41433-019-0593-x
65. Dave V. P., Pathengay A., Braimah I. Z., Panchal B., Sharma S., Pappuru R. R., Mathai A., Tyagi M., Narayanan R., Jalali S., Das T. Enterococcus endophthalmitis: clinical settings, antimicrobial susceptibility, and management outcomes. Retina. 2020, 40 (5), 898–902. https://doi.org/10.1097/IAE.0000000000002462
66. Ross M., Desch?nes J. Practice patterns in the interdisciplinary management of corneal abrasions. Can. J. Ophthalmol. 2017, 52 (6), 548–551. https://doi.org/10.1016/j. jcjo.2017.03.016
67. Folkman J., Weisz P. B., Joullie M. M. Control of angiogenesis with synthetic heparin substitutes. Science. 1989, V. 243, P. 1490–1495. https://doi.org/10.1126/science.2467380
68. Avery R. L., Connor T. B., Farazdaghi M. Systemic amiloride inhibits experimentally induced neovascularization. Arch. Ophthalmol. 1990, V. 108, P. 1474– 1478. https://doi.org/10.1001/archopht.1990.01070120122041
69. Romani P., Valcarcel-Jimenez L., Frezza C., Dupont S. Crosstalk between mechanotransduction and metabolism. Nat. Rev. Mol. Cell Biol. 2021, 22 (1), 22–38. https://doi.org/10.1038/s41580-020-00306-w
70. Deutsch T. A., Hughes W. F. Suppressive effects of indomethacin on thermally induced neovascularization of rabbit corneas. Am. J. Ophthalmol. 1979, V. 87, P. 536–540. https://doi.org/10.1016/0002-9394(79)90245-9
71. Duffin R. M., Weissman B. A., Gtasser D. B. Flurbiprofen in the treatment of corneal neovascularization induced by contact lenses. Am. J. Ophthalmol. 1982, V. 93, P. 607–611. https://doi.org/10.1016/S0002-9394(14)77376-3
72. Verbey N. L. J., Van Haeringen N. J., De Jong P. R. V. M. Modulation of immunogenic keratitis in rabbits by topical administration of inhibitors of lipoxygenase and cyclooxygenase. Curr. Eye Res. 1988, V. 7, P. 361–365. https://doi.org/10.3109/02713688809031785
73. Hanahan D., Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. J. Cell. 1996, V. 86, P. 353–364. https://doi.org/10.1016/S0092-8674(00)80108-7
74. Plou?t J., Moro F., Bertagnolli S., Coldeboeuf N., Mazarguil H., Clamens S., Bayard F. Extracellular cleavage of the vascular endothelial growth factor 189-amino acid form by urokinase is required for its mitogenic effect. J. Biol. Chem. 1997, V. 272, P. 13390–13396. https://doi.org/10.1074/jbc.272.20.13390
75. Kim J. H., Kim J. C., Shin S. H., Chang S. I., Lee H. S., Chung S. I. The inhibitory effects of recombinant plasminogen kringle 1-3 on the neovascularization of rabbit cornea induced by angiogenin, bFGF, and VEGF. Exp. Mol. Med. 1999, V. 31, P. 203–209. https://doi.org/10.1038/emm.1999.33
76. Sack R. A., Beaton A. R., Sathe S. Diurnal variations in angiostatin in human tear fluid: a possible role in prevention of corneal neovascularization. Curr. Eye Res. 1999, 18 (3), 186–193. https://doi.org/10.1076/ceyr.18.3.186.5367
77. Wang H., Berman M., Law M. Latent and active plasminogen activator in corneal ulceration. Invest. Ophthalmol. Vis. Sci. 1985, V. 26, P. 511–524. PMID: 8578451
78. Chesnokova N. B., Aisina R. B., Mukhametova L. I., Pavlenko T. A., Gulin D. A., Beznos O. V. Fibrinolysis components and angiogenesis regulation by example of burn-induced corneal neovascularization in rabbits. Vestn. Oftalmol. 2012, 128 (4), 62–65. PMID: 22994111
79. Ahmed A., Berati H., Nalan A., Aylin S. Effect of bevacizumab on corneal neovascularization in experimental rabbit model. Clin. Experiment. Ophthalmol. 2009, 37 (7), 370–376. https://doi.org/10.1111/j.1442-9071.2009.02112.x
80. Zhang Z., Ma J. X., Gao G., Li C., Luo L., Zhang M., Yang W., Jiang A., Kuang W., Xu L., Chen J., Liu Z. Plasminogen kringle 5 inhibits alkali-burn-induced corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 2005, 46 (11), 4062–4071. https://doi.org/10.1167/iovs.04-1330
81. Ambati B. K., Joussen A. M., Ambati J., Moromizato Y., Guha C., Javaherian K., Gillies S., O’Reilly M. S., Adamis A. P. Angiostatin inhibits and regresses corneal neovascularization. Arch. Ophthalmol. 2002, 120 (8), 1063–1068. https://doi.org/10.1001/archopht.120.8.1063
82. Albini A., Brigati C., Ventura A., Lorusso G., Pinter M., Morini M., Mancino A., Sica A., Noonan D. M. Angiostatin anti-angiogenesis requires IL-12: the innate immune system as a key target. J. Transl. Med. 2009, V. 14, P. 5–7. https://doi.org/10.1186/1479-5876- 7-5
83. Murata M., Nakagawa M., Takahashi S. Inhibitory effects of plasminogen fragment on experimentally induced neovascularization of rat corneas. Graefe’s Arch. Clin. Exp. Ophthalmol. 1997, V. 235, P. 584–586. https://doi.org/10.1007/BF00947088
84. Vassalli J. D., Sappino A. P., Belin D. The plasminogen activator/plasmin system. J. Clin. Invest. 1991, V. 88, P. 1067–1072. https://doi.org/10.1172/JCI115405
85. Vogten J. M., Reijerkerk A., Meijers J. C., Voest E. E., Borel Rinkes I. H., Gebbink M. F. The role of the fibrinolytic system in corneal angiogenesis. Angiogenesis. 2003, 6 (4), 311–316. https://doi.org/10.1023/B:AGEN.0000029414.24060.fe
86. Mignatti P., Rifkin D. B. Plasminogen activators and angiogenesis. Curr. Top. Microbiol. Immun. 1996, V. 213, P. 33–50. https://doi.org/10.1007/978-3-642-61107-0_3
87. O’Reilly M. S., Holmgren L., Chert C., Folkman J. Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat. Med. 1996, V. 2, P. 689–692. https://doi.org/10.1038/nm0696-689
88. Gao G., Li Y., Gee S., Dudley A., Fant J., Crosson C., Ma J. X. Down-regulation of vascular endothelial growth factor and upregulation of pigment epithelium-derived factor: a possible mechanism for the antiangiogenic activity of plasminogen kringle 5. J. Biol. Chem. 2002, V. 277, P. 9492–9497. https://doi.org/10.1074/jbc.M108004200
89. Ng E. W. M., Adamis A. P. Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. Can. J. Ophthalmol. 2005, V. 40, P. 352–368. https://doi.org/10.1016/S0008-4182(05)80078-X
90. Miller J. W., Adamis A. P., Aiello L. P. Vascular endothelial growth factor in ocular neovascularization and proliferative diabetic retinopathy. Diabetes Metab. Rev. 1997, 13 (1), 37–50. https://doi.org/10.1002/(SICI)1099-0895(199703)13:1<37::AID-DMR174>3.0.CO;2-K
91. Buch P. K., Bainbridge J. W., Ali R. R. AAVmediated gene therapy for retinal disorders. Gene Therapy. 2008, V. 15, P. 849–857. https://doi.org/10.1038/gt.2008.66
92. Zhang D., Kaufman P. L., Gao G., Saunders R. A., Ma J. X. Intravitreal injection of plasminogen kringle 5, an endogenous angiogenic inhibitor, arrests retinal neovascularization in rats. Diabetologia. 2001, 44 (6), 757–765. https://doi.org/10.1007/s001250051685
93. Ma J., Li Ch., Shao Ch., Gao G., Yang X. Decreased K5 receptor expression in the retina, a potential pathogenic mechanism for diabetic retinopathy. Mol. Vis. 2012, V. 18, P. 330–336. PMID: 22355244
94. Ferrara N., Gerber H. P., LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003, 9 (6), 669–676. https://doi.org/10.1038/nm0603-669
95. Gao G. Q., Li Y., Zhang D. C., Gee S., Crosson C., Ma J. X. Unbalanced expression of VEGF and PEDF in ischemia-induced retinal neovascularization. FEBS Lett. 2001, V. 489, P. 270–276. https://doi.org/10.1016/S0014-5793(01)02110-X
96. Aiello L. P., Avery R. L., Arrigg P. G., Keyt B. A., Jampel H. D., Shah S. T., Pasquale L. R., Thieme H., Iwamoto M. A., Park J. E. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Engl. J. Med. 1994, V. 331, P. 1480–1487. https://doi.org/10.1056/NEJM199412013312203
97. Pe’er J., Folberg R., Itin A., Gnessin H., Hemo I., Keshet E. Vascular endothelial growth factor upregulation in human central retinal vein occlusion. Ophthalmology. 1998, 105 (3), 412–416. https://doi.org/10.1016/S0161-6420(98)93020-2
98. Pierce E. A., Avery R. L., Foley E. D., Aiello L. P., Smith L. E. Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization. Proc. Natl. Acad. Sci. U. S. A. 1995, V. 92, P. 905–909. https://doi.org/10.1073/pnas.92.3.905
99. Adamis A. P., Miller J. W., Bernal M. T., D’Amico D. J., Folkman J., Yeo T. K., Yeo K. T. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am. J. Ophthalmol. 1994, V. 118, P. 445– 450. https://doi.org/10.1016/S0002-9394(14)75794-0
100. Umeda N., Ozaki H., Hayashi H., MiyajimaUchida H., Oshima K. Colocalization of Tie2, angiopoietin 2 and vascular endothelial growth factor in fibrovascular membrane from patients with retinopathy of prematurity. Ophthalmic Res. 2003, 35 (4), 217–223. https://doi.org/10.1159/000071173
101. Stellmach V., Crawford S. E., Zhou W., Bouck N. Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epitheliumderived factor. Proc. Natl. Acad. Sci. U. S. A. 2001, V. 98, P. 2593–2597. https://doi.org/10.1073/pnas.031252398
102. Redlitz A., Daum G., Sage E. H. Angiostatin diminishes activation of the mitogenactivated protein kinases ERK-1 and ERK-2 in human dermal microvascular endothelial cells. J. Vasc. Res. 1999, V. 36, P, 28–34. https://doi.org/10.1159/000025623
103. Jacobson B., Basu P. K., Hasany S. M. Vascular endothelial cell growth inhibitor of normal and pathologic human vitreous. Arch. Ophthalmol. 1984, V. 102, P. 1543–1545. https://doi.org/10.1001/archopht.1984.01040031259031
104. Glaser B. M., Campochiaro P. A., Davis J. L., Sato M. Retinal pigment epithelial cells release an inhibitor of neovascularization. Arch. Ophthalmol. 1985, V. 103, P. 1870–1875. https://doi.org/10.1001/archopht.1985.01050120104029
105. Punglia R. S., Lu M., Hsu J., Kuroki M., Tolentino M. J., Keough K., Levy A. P., Levy N. S., Goldberg M. A., D’Amato R. J., Adamis A. P. Regulation of vascular endothelial growth factor expression by insulin-like growth factor I. Diabetes. 1997, V. 46, P. 1619–1626. https://doi.org/10.2337/diabetes.46.10.1619
106. Morwenna S., Ratcliffe W. P. Mammalian oxygen sensing and hypoxia inducible factor-1. Int. J. Biochem. Cell Biol. 1997, V. 29, P. 1419–1432. https://doi.org/10.1016/S1357-2725(97)00129-5
107. Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J. Mol. Med. 1999, V. 77, P. 527–543. https://doi.org/10.1007/s001099900019
108. Seko Y., Takahashi N., Tobe K., Ueki K., Kadowaki T., Yazaki Y. Vascular endothelial growth factor (VEGF) activates Raf-1, mitogen-activated protein (MAP) kinases, and S6 kinase (p90rsk) in cultured rat cardiac myocytes. J. Cell. Physiol. 1998, V. 175, P. 239–246. https://doi.org/10.1002/(SICI)1097-4652(199806)175:3<239::AID-JCP1>3.0.CO;2-P
109. Eliceiri B. P., Klemke R., Stromblad S., Cheresh D. A. Integrin alphavbeta3 requirement for sustained mitogenactivated protein kinase activity during angiogenesis. J. Cell Biol. 1998, V. 140, P. 1255–1263. https://doi.org/10.1083/jcb.140.5.1255
110. Tarui T., Miles L. A., Takada Y. Specific interaction of angiostatin with integrin alpha(v)beta(3) in endothelial cells. J. Biol. Chem. 2001, V. 276, P. 39562–39568. https://doi.org/10.1074/jbc.M101815200