SRPK1 inhibition modulates VEGF splicing to reduce pathological neovascularization in a rat model of retinopathy of prematurity

Investigative Ophthalmology and Visual Science

Volumn 54, Issue 8, 2013, Pages 5797-5806

  Gammons, Melissa V R ^a   Dick, Andrew D ^a   Harper, Steven J ^a   Bates, David O ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

Angiogenesis; Retinopathy of prematurity; Splicing; VEGF

Indexed keywords

G6 31; PROTEIN KINASE; PROTEIN KINASE INHIBITOR; RECOMBINANT VASCULOTROPIN; SERINE ARGININE PROTEIN KINASE 340; UNCLASSIFIED DRUG; VASCULOTROPIN ANTIBODY;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL MIGRATION; CELL PROTECTION; CONTROLLED STUDY; DENSITOMETRY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROCESSING; RAT; RETINA NEOVASCULARIZATION; RETROLENTAL FIBROPLASIA; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SURVIVAL RATE; WESTERN BLOTTING;

ANGIOGENESIS; RETINOPATHY OF PREMATURITY; SPLICING; VEGF;

ANIMALS; BLOTTING, WESTERN; CELLS, CULTURED; DISEASE MODELS, ANIMAL; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; HUMANS; INFANT, NEWBORN; INJECTIONS, INTRAOCULAR; NIACINAMIDE; PIPERIDINES; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; RATS; RATS, SPRAGUE-DAWLEY; RETINAL NEOVASCULARIZATION; RETINOPATHY OF PREMATURITY; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84883206420     PISSN: 01460404     EISSN: 15525783     Source Type: Journal    
DOI: 10.1167/iovs.13-11634     Document Type: Article

References (81)

1. Ashton N, Ward B, Serpell G. Role of oxygen in the genesis of retrolental fibroplasia-a preliminary report. Br J Ophthalmol. 1953;37:513-520.
2. Gariano RF, Gardner TW. Retinal angiogenesis in development and disease. Nature. 2005;438:960-966.
3. Patz A, Fine SL, Finkelstein D, Yassur Y. Diseases of macula-diagnosis and management of choroidal neovascularization. Trans Am Acad Ophthalmol Otolaryngol. 1977;83:468-475.
4. Chanling T, Stone J. Retinopathy of prematurity-origins in the architecture of the retina. Prog Retin Res. 1993;12:155-178.
5. Hardy P, Dumont I, Bhattacharya M, et al. Oxidants, nitric oxide and prostanoids in the developing ocular vasculature: a basis for ischemic retinopathy. Cardiovasc Res. 2000;47:489-509.
6. Penn JS, Thum LA. The rat as an animal model for retinopathy of prematurity. Prog Clin Biol Res. 1989;314:623-642.
7. Foos RY. Chronic retinopathy of prematurity. Ophthalmology. 1985;92:563-574.
8. Katzman G, Satish M, Krishnan V. Hypoxemia and retinopathy of prematurity. Pediatrics. 1987;80:972-972.
9. Biglan AW, Brown DR, Reynolds JD, Milley JR. Risk-factors associated with retrolental fibroplasia. Ophthalmology. 1984; 91:1504-1511.
10. Barnett JM, Yanni SE, Penn JS. The development of the rat model of retinopathy of prematurity. Doc Ophthalmol. 2010; 120:3-12.
11. Qazi Y, Maddula S, Ambati BK. Mediators of ocular angiogenesis. J Genet. 2009;88:495-515.
12. Ozaki H, Yu AY, Della N, et al. Hypoxia inducible factor-1 alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression. Invest Ophthalmol Vis Sci. 1999; 40:182-189.
13. Good WV, Gendron RL. Retinopathy of prematurity: gone today, here tomorrow? Clin Exp Ophthalmol. 2005;33:339-340.
14. Foxton RH, Finkelstein A, Vijay S, et al. VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma. Am J Pathol. 2013;182:1379-1390.
15. Nishijima K, Ng Y-S, Zhong L, et al. Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol. 2007;171:53-67.
16. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nature Med. 2003;9:669-676.
17. Vincenti V, Cassano C, Rocchi M, Persico G. Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation. 1996;93:1493-1495.
18. Jingjing L, Xue Y, Agarwal N, Roque RS. Human Muller cells express VEGF183, a novel spliced variant of vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1999; 40:752-759.
19. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth-factor is a secreted angiogenic mitogen. Science. 1989;246:1306-1309.
20. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. Faseb J. 1999;13:9-22.
21. Tischer E, Gospodarowicz D, Mitchell R, et al. Vascular endothelial growth-factor-a new member of the plateletderived growth-factor gene family. Biochem Biophys Res Commun. 1989;165:1198-1206.
22. Harper SJ, Bates DO. VEGF-A splicing: the key to antiangiogenic therapeutics? Nat Rev Cancer. 2008;8:880-887.
23. Woolard J, Wang WY, Bevan HS, et al. VEGF165b, an inhibitory vascular endothelial growth factor splice variant: mechanism of action, in vivo effect on angiogenesis and endogenous protein expression. Cancer Res. 2004;64:7822-7835.
24. Bates DO, Cui TG, Doughty JM, et al. VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is downregulated in renal cell carcinoma. Cancer Res. 2002;62:4123-4131.
25. Cebe-Suarez S, Zehnder-Fjallman A, Ballmer-Hofer K. The role of VEGF receptors in angiogenesis; complex partnerships. Cell Mol Life Sci. 2006;63:601-615.
26. Kawamura H, Li XJ, Goishi K, et al. Neuropilin-1 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organization. Blood. 2008;112:3638-3649.
27. Amin EM, Oltean S, Hua J, et al. WT1 mutants reveal SRPK1 to be a downstream angiogenesis target by altering VEGF splicing. Cancer Cell. 2011;20:768-780.
28. Nowak DG, Amin EM, Rennel ES, et al. Regulation of vascular endothelial growth factor (VEGF) splicing from pro-angiogenic to anti-angiogenic isoforms: a novel therapeutic strategy for angiogenesis. J Biol Chem. 2010;285:5532-5540.
29. Nowak DG, Woolard J, Amin EM, et al. Expression of pro-and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors. J Cell Sci. 2008;121:3487-3495.
30. Aubol BE, Chakrabarti S, Ngo J, et al. Processive phosphorylation of alternative splicing factor/splicing factor 2. Proc Natl Acad Sci U S A. 2003;100:12601-12606.
31. Kataoka N, Bachorik JL, Dreyfuss G. Transportin-SR, a nuclear import receptor for SR proteins. J Cell Biol. 1999;145.
32. Ngo JCK, Chakrabarti S, Ding JH, et al. Interplay between SRPK and Clk/Sty kinases in phosphorylation of the splicing factor ASF/SF2 is regulated by a docking motif in ASF/SF2. Mol Cell. 2005;20:77-89.
33. Fukuhara T, Hosoya T, Shimizu S, et al. Utilization of host SR protein kinases and RNA-splicing machinery during viral replication. Proc Natl Acad Sci U S A. 2006;103:11329-11333.
34. Smith LEH, Wesolowski E, McLellan A, et al. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994;35: 101-111.
35. Penn JS, Henry MM, Tolman BL. Exposure to alternating hypoxia and hyperoxia causes severe proliferative retinopathy in the newborn rat. Ped Res. 1994;36:724-731.
36. Cunningham S, Fleck BW, Elton RA, McIntosh N. Transcutaneous oxygen levels in retinopathy of prematurity. Lancet. 1995;346:1464-1465.
37. Liu K, Akula JD, Falk C, Hansen RM, Fulton AB. The retinal vasculature and function of the neural retina in a rat model of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2006; 47:2639-2647.
38. Hartnett ME, Martiniuk D, Byfield G, Geisen P, Zeng G, Bautch VL. Neutralizing VEGF decreases tortuosity and alters endothelial cell division orientation in arterioles and veins in a rat model of ROP: relevance to plus disease. Invest Ophthalmol Vis Sci. 2008;49:3107-3114.
39. Hartnett ME, Martiniuk DJ, Saito Y, Geisen P, Peterson LJ, McColm JR. Triamcinolone reduces neovascularization, capillary density and IGF-1 receptor phosphorylation in a model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 2006; 47:2639-2647.
40. Penn JS, Tolman BL, Lowery LA. Variable oxygen exposure causes preretinal neovascularization in the newborn rat. Invest Ophthalmol Vis Sci. 1993;34:576-585.
41. Geisen P, Peterson LJ, Martiniuk D, Uppal A, Saito Y, Hartnett ME. Neutralizing antibody to VEGF reduces intravitreous neovascularization and may not interfere with ongoing intraretinal vascularization in a rat model of retinopathy of prematurity. Mol Vis. 2008;14:345-357.
42. Young TL, Anthony DC, Pierce E, Foley E, Smith LE. Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity. J AAPOS 1997;1:105-110.
43. Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins-identification by morphologic and immunological criteria. J Clin Invest. 1973;52:2745-2756.
44. Konopatskaya O, Churchill AJ, Harper SJ, Bates DO, Gardiner TA. VEGF(165)b, an endogenous C-terminal splice variant of VEGF, inhibits retinal neovascularization in mice. Mol Vis. 2006;12:626-632.
45. Hartmann JS, Thompson H, Wang H, et al. Expression of vascular endothelial growth factor and pigment epithelialderived factor in a rat model of retinopathy of prematurity. Mol Vis. 2011;17:1577-1587.
46. McColm J, Geisen P, Hartnett M. VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: Relevance to clinical ROP. Mol Vis. 2004;10:512-520.
47. Werdich XQ, Penn JS. Specific involvement of Src family kinase activation in the pathogenesis of retinal neovascularization. Invest Ophthalmol Vis Sci. 2006;47:5047-5056.
48. Zhao M, Shi X, Liang J, et al. Expression of pro-and antiangiogenic isoforms of VEGF in the mouse model of oxygeninduced retinopathy. Exp Eye Res. 2011;93:921-926.
49. Baba T, McLeod DS, Edwards MM, et al. VEGF 165b in the developing vasculatures of the fetal human eye. Dev Dynam. 2011;241:595-607.
50. Zimmermann RC, Hartman T, Kavic S, et al. Vascular endothelial growth factor receptor 2-mediated angiogenesis is essential for gonadotropin-dependent follicle development. J Clin Invest. 2003;112:659-669.
51. Bates DO, Jones ROP. The role of vascular endothelial growth factor in wound healing. Int J Low Extrem Wounds. 2003;2: 107-120.
52. Pritchard-Jones RO, Dunn DBA, Qiu Y, et al. Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma. Br J Cancer. 2007;97:223-230.
53. Das A, Fanslow W, Cerretti D, Warren E, Talarico N, McGuire P. Angiopoietin/Tek interactions regulate MMP-9 expression and retinal neovascularization. Lab Invest. 2003;83:1637-1645.
54. Manetti M, Guiducci S, Romano E, et al. Overexpression of VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, leads to insufficient angiogenesis in patients with systemic sclerosis. Circ Res. 2011;109:e14-e26.
55. Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. 2007;100:782-794.
56. Rennel ES, Waine E, Guan H, et al. The endogenous antiangiogenic VEGF isoform, VEGF(165)b inhibits human tumour growth in mice. Br J Cancer. 2008;98:1250-1257.
57. Hua J, Spee C, Kase S, et al. Recombinant human VEGF(165)b inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2010;51:4282-4288.
58. Magnussen AL, Rennel ES, Hua J, et al. VEGF-A(165)b is cytoprotective and antiangiogenic in the retina. Invest Ophthalmol Vis Sci. 2010;51:4273-4281.
59. Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Disc. 2004;3:391-400.
60. Qiu Y, Bevan H, Weeraperuma S, et al. Mammary alveolar development during lactation is inhibited by the endogenous antiangiogenic growth factor isoform, VEGF165b. Faseb J. 2008;22:1104-1112.
61. Penn JS, McCollum GW, Barnett JM, Werdich XQ, Koepke KA, Rajaratnam VS. Angiostatic effect of penetrating ocular injury: role of pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2006;47:405-414.
62. Saito Y, Uppal A, Byfield G, Budd S, Hartnett ME. Activated NAD(P)H oxidase from supplemental oxygen induces neovascularization independent of VEGF in retinopathy of prematurity model. Invest Ophthalmol Vis Sci. 2008;49:1591-1598.
63. Freedman SF, Kylstra JA, Capowski JJ, Realini TD, Rich C, Hunt D. Observer sensitivity to retinal vessel diameter and tortuosity in retinopathy of prematurity: a model system. J Pediatr Ophthalmol Strabismus. 1996;33:248-254.
64. Werdich XQ, McCollum GW, Rajaratnam VS, Penn JS. Variable oxygen and retinal VEGF levels: correlation with incidence and severity of pathology in a rat model of oxygen-induced retinopathy. Exp Eye Res. 2004;79:623-630.
65. Chen J, Smith LEH. Retinopathy of prematurity. Angiogenesis. 2007;10:133-140.
66. Connolly BP, Ng EYJ, McNamara JA, Regillo CD, Vander JF, Tasman W. A comparison of laser photocoagulation with cryotherapy for threshold retinopathy of prematurity at 10 years-part 2. Refractive outcome. Ophthalmology. 2002;109: 936-941.
67. Ng EYJ, Connolly BP, McNamara JA, Regillo CD, Vander JF, Tasman W. A comparison of laser photocoagulation with cryotherapy for threshold retinopathy of prematurity at 10 years-part 1. Visual function and structural outcome. Ophthalmology. 2002;109:928-934.
68. Lambert SR, Capone A, Cingle KA, Drack AV. Cataract and phthisis bulbi after laser photoablation for threshold retinopathy of prematurity. Am J Ophthalmol. 2000;129:585-591.
69. O'Neil JW, Hutchinson AK, Saunders RA, Wilson ME. Acquired cataracts after argon laser photocoagulation for retinopathy of prematurity. J AAPOS. 1998;2:48-51.
70. Aiello LP, Pierce EA, Foley ED, et al. Suppression of retinal neovascularization in-vivo by inhibition of vascular endothelial growth-factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A. 1995;92:10457-10461.
71. Sato T, Kusaka S, Shimojo H, Fujikado T. Vitreous levels of erythropoietin and vascular endothelial growth factor in eyes with retinopathy of prematurity. Ophthalmology. 2009;116: 1599-1603.
72. Smith LEH, Shen W, Perruzzi C, et al. Regulation of vascular endothelial growth factor-dependent retinal neovascularization by insulin-like growth factor-1 receptor. Nat Med. 1999;5: 1390-1395.
73. Lee JY, Chae JB, Yang SJ, Yoon YH, Kim JG Effects of intravitreal bevacizumab and laser in retinopathy of prematurity therapy on the development of peripheral retinal vessels. Graefes Arch Clin Exp Ophthalmol. 2010;248:1257-1262.
74. Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+retinopathy of prematurity. New Engl J Med. 2011; 364:603-615.
75. Moshfeghi DM, Berrocal AM. Retinopathy of prematurity in the time of bevacizumab: incorporating the BEAT-ROP results into clinical practice. Ophthalmology. 2011;118:1227-1228.
76. Gilbert CE, Zin A, Darlow B. Bevacizumab for retinopathy of prematurity. New Engl J Med. 2011;364:603-615.
77. Raizada S, Al Kandari J, Al Sabti K. Will the BEAT-ROP study results really beat ROP? Invest Ophthalmol Vis Sci. 2011;52: 9288-9289.
78. Hara A, Wada T, Furuichi K, et al. Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glornerulonephritis. Kidney Int. 2006;69: 1986-1995.
79. Pierce EA, Foley ED, Smith LEH. Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol. 1996;114:1219-1228.
80. Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K; SEVENUP Study Group. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP) [published online ahead of print May 3, 2013]. Ophthalmology. doi:10.1016/j.ophtha.2013.03.046.
81. Beazley Long N, Hulse RP, Hua J, et al. The anti-angiogenic isoform of VEGF, VEGF165b, is neuroprotective in vivo. Am J Pathol. In press.