Blue-violet light decreases VEGFa production in an in vitro model of AMD


Autoři: Mélanie Marie aff001;  Pauline Gondouin aff001;  Delphine Pagan aff001;  Coralie Barrau aff002;  Thierry Villette aff002;  José Sahel aff001;  Serge Picaud aff001
Působiště autorů: Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France aff001;  Essilor International R&D, Charenton-le-Pont, France aff002;  Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223839

Souhrn

Blue light is an identified risk factor for age-related macular degeneration (AMD). The production of vascular endothelial growth factor (VEGF), leading to neovascularization, is a major complication of the wet form of this disease. We investigated how blue light affects VEGF expression and secretion using A2E-loaded retinal pigment epithelium (RPE) cells, a cell model of AMD. Incubation of RPE cells with A2E resulted in a significant increase in VEGF mRNA and, intracellular and secreted VEGF protein levels, but not mRNA levels of VEGFR1 or VEGFR2. Blue light exposure of A2E-loaded RPE cells resulted in a decrease in VEGF mRNA and protein levels, but an increase in VEGFR1 levels. The toxicity of 440 nm light on A2E-loaded RPE cells was enhanced by VEGF supplementation. Our results suggest that age-related A2E accumulation may result in VEGF synthesis and release. This synthesis of VEGF, which enhances blue light toxicity for the RPE cells, is itself suppressed by blue light. Anti-VEGF therapy may therefore improve RPE survival in AMD.

Klíčová slova:

Apoptosis – Light – Macular degeneration – Messenger RNA – Retina – Sunlight – Toxicity – White light


Zdroje

1. Bhutto I, Lutty G. Understanding age-related macular degeneration (AMD): relationships between the photoreceptor/retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. Mol Aspects Med. 2012;33(4):295–317. doi: 10.1016/j.mam.2012.04.005 22542780

2. Sui GY, Liu GC, Liu GY, Gao YY, Deng Y, Wang WY, et al. Is sunlight exposure a risk factor for age-related macular degeneration? A systematic review and meta-analysis. Br J Ophthalmol. 2013;97(4):389–394. doi: 10.1136/bjophthalmol-2012-302281 23143904

3. Miller JW. VEGF: From Discovery to Therapy: The Champalimaud Award Lecture. Transl Vis Sci Technol. 2016;5(2):9. doi: 10.1167/tvst.5.2.9 26981331

4. Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res. 2008;27(4):331–371. doi: 10.1016/j.preteyeres.2008.05.001 18653375

5. Miller JW. Beyond VEGF-The Weisenfeld Lecture. Invest Ophthalmol Vis Sci. 2016;57(15):6911–6918. doi: 10.1167/iovs.16-21201 28027565

6. Stuttfeld E, Ballmer-Hofer K. Structure and function of VEGF receptors. IUBMB Life. 2009;61(9):915–922. doi: 10.1002/iub.234 19658168

7. Holmes DI, Zachary IC. Vascular endothelial growth factor regulates stanniocalcin-1 expression via neuropilin-1-dependent regulation of KDR and synergism with fibroblast growth factor-2. Cell Signal. 2008;20(3):569–579. doi: 10.1016/j.cellsig.2007.11.009 18164591

8. Schick T, Ersoy L, Lechanteur YT, Saksens NT, Hoyng CB, den Hollander AI, et al. History of Sunlight Exposure Is a Risk Factor for Age-Related Macular Degeneration. Retina. 2016;36(4):787–790. doi: 10.1097/IAE.0000000000000756 26441265

9. Lambert NG, ElShelmani H, Singh MK, Mansergh FC, Wride MA, Padilla M, et al. Risk factors and biomarkers of age-related macular degeneration. Prog Retin Eye Res. 2016;54:64–102. doi: 10.1016/j.preteyeres.2016.04.003 27156982

10. Augood CA, Vingerling JR, de Jong PT, Chakravarthy U, Seland J, Soubrane G, et al. Prevalence of age-related maculopathy in older Europeans: the European Eye Study (EUREYE). Arch Ophthalmol. 2006;124(4):529–535. doi: 10.1001/archopht.124.4.529 16606879

11. Cruickshanks KJ, Klein R, Klein BE, Nondahl DM. Sunlight and the 5-year incidence of early age-related maculopathy: the beaver dam eye study. Arch Ophthalmol. 2001;119(2):246–250. 11176987

12. Young RW. Sunlight and age-related eye disease. J Natl Med Assoc. 1992;84(4):353–358. 1507250

13. Taylor HR, West S, Munoz B, Rosenthal FS, Bressler SB, Bressler NM. The long-term effects of visible light on the eye. Arch Ophthalmol. 1992;110(1):99–104. doi: 10.1001/archopht.1992.01080130101035 1731731

14. Fletcher AE, Bentham GC, Agnew M, Young IS, Augood C, Chakravarthy U, et al. Sunlight exposure, antioxidants, and age-related macular degeneration. Arch Ophthalmol. 2008;126(10):1396–1403. doi: 10.1001/archopht.126.10.1396 18852418

15. Butt AL, Lee ET, Klein R, Russell D, Ogola G, Warn A, et al. Prevalence and risks factors of age-related macular degeneration in Oklahoma Indians: the Vision Keepers Study. Ophthalmology. 2011;118(7):1380–1385. doi: 10.1016/j.ophtha.2010.11.007 21310490

16. Loane E, Kelliher C, Beatty S, Nolan JM. The rationale and evidence base for a protective role of macular pigment in age-related maculopathy. Br J Ophthalmol. 2008;92(9):1163–1168. doi: 10.1136/bjo.2007.135566 18669545

17. Snodderly DM. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am J Clin Nutr. 1995;62(6 Suppl):1448S–1461S.

18. Mainster MA, Turner PL. Blue-blocking IOLs decrease photoreception without providing significant photoprotection. Surv Ophthalmol. 2010;55(3):272–289. doi: 10.1016/j.survophthal.2009.07.006 19883931

19. Kijlstra A, Tian Y, Kelly ER, Berendschot TT. Lutein: more than just a filter for blue light. Prog Retin Eye Res. 2012;31(4):303–315. doi: 10.1016/j.preteyeres.2012.03.002 22465791

20. Jia YP, Sun L, Yu HS, Liang LP, Li W, Ding H, et al. The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and Cognition Diseases. Molecules. 2017;22(4).

21. Lima VC, Rosen RB, Farah M. Macular pigment in retinal health and disease. Int J Retina Vitreous. 2016;2:19. doi: 10.1186/s40942-016-0044-9 27847637

22. Loskutova E, Nolan J, Howard A, Beatty S. Macular pigment and its contribution to vision. Nutrients. 2013;5(6):1962–1969. doi: 10.3390/nu5061962 23760061

23. Junghans A, Sies H, Stahl W. Macular pigments lutein and zeaxanthin as blue light filters studied in liposomes. Arch Biochem Biophys. 2001;391(2):160–164. doi: 10.1006/abbi.2001.2411 11437346

24. Sparrow JR, Boulton M. RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res. 2005;80(5):595–606. doi: 10.1016/j.exer.2005.01.007 15862166

25. Iriyama A, Inoue Y, Takahashi H, Tamaki Y, Jang WD, Yanagi Y. A2E, a component of lipofuscin, is pro-angiogenic in vivo. J Cell Physiol. 2009;220(2):469–475. doi: 10.1002/jcp.21792 19418485

26. Iriyama A, Fujiki R, Inoue Y, Takahashi H, Tamaki Y, Takezawa S, et al. A2E, a pigment of the lipofuscin of retinal pigment epithelial cells, is an endogenous ligand for retinoic acid receptor. J Biol Chem. 2008;283(18):11947–11953. doi: 10.1074/jbc.M708989200 18326047

27. Suter M, Reme C, Grimm C, Wenzel A, Jaattela M, Esser P, et al. Age-related macular degeneration. The lipofusion component N-retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells. J Biol Chem. 2000;275(50):39625–39630. doi: 10.1074/jbc.M007049200 11006290

28. Boulton M, Rozanowska M, Rozanowski B. Retinal photodamage. J Photochem Photobiol B. 2001;64(2–3):144–161. doi: 10.1016/s1011-1344(01)00227-5 11744401

29. Rozanowska M, Pawlak A, Rozanowski B, Skumatz C, Zareba M, Boulton ME, et al. Age-related changes in the photoreactivity of retinal lipofuscin granules: role of chloroform-insoluble components. Invest Ophthalmol Vis Sci. 2004;45(4):1052–1060. doi: 10.1167/iovs.03-0277 15037568

30. Wihlmark U, Wrigstad A, Roberg K, Nilsson SE, Brunk UT. Lipofuscin accumulation in cultured retinal pigment epithelial cells causes enhanced sensitivity to blue light irradiation. Free Radic Biol Med. 1997;22(7):1229–1234. doi: 10.1016/s0891-5849(96)00555-2 9098097

31. Schutt F, Davies S, Kopitz J, Holz FG, Boulton ME. Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Invest Ophthalmol Vis Sci. 2000;41(8):2303–2308. 10892877

32. Sparrow JR, Nakanishi K, Parish CA. The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci. 2000;41(7):1981–1989. 10845625

33. Davies S, Elliott MH, Floor E, Truscott TG, Zareba M, Sarna T, et al. Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells. Free Radic Biol Med. 2001;31(2):256–265. doi: 10.1016/s0891-5849(01)00582-2 11440838

34. Sparrow JR, Cai B. Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by Bcl-2. Invest Ophthalmol Vis Sci. 2001;42(6):1356–1362. 11328751

35. Nilsson SE, Sundelin SP, Wihlmark U, Brunk UT. Aging of cultured retinal pigment epithelial cells: oxidative reactions, lipofuscin formation and blue light damage. Doc Ophthalmol. 2003;106(1):13–16. doi: 10.1023/a:1022419606629 12675480

36. Sparrow JR, Cai B, Fishkin N, Jang YP, Krane S, Vollmer HR, et al. A2E, a fluorophore of RPE lipofuscin: can it cause RPE degeneration? Adv Exp Med Biol. 2003;533:205–211. doi: 10.1007/978-1-4615-0067-4_26 15180266

37. Westlund BS, Cai B, Zhou J, Sparrow JR. Involvement of c-Abl, p53 and the MAP kinase JNK in the cell death program initiated in A2E-laden ARPE-19 cells by exposure to blue light. Apoptosis. 2009;14(1):31–41. doi: 10.1007/s10495-008-0285-7 19052872

38. van der Burght BW, Hansen M, Olsen J, Zhou J, Wu Y, Nissen MH, et al. Early changes in gene expression induced by blue light irradiation of A2E-laden retinal pigment epithelial cells. Acta Ophthalmol. 2013;91(7):e537–545. doi: 10.1111/aos.12146 23742627

39. Liu Y, Song X, Zhang D, Zhou F, Wang D, Wei Y, et al. Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells. Br J Nutr. 2012;108(1):16–27. doi: 10.1017/S000711451100523X 22018225

40. Hui S, Yi L, Fengling QL. Effects of light exposure and use of intraocular lens on retinal pigment epithelial cells in vitro. Photochem Photobiol. 2009;85(4):966–969. doi: 10.1111/j.1751-1097.2008.00506.x 19192204

41. Zhou J, Cai B, Jang YP, Pachydaki S, Schmidt AM, Sparrow JR. Mechanisms for the induction of HNE- MDA- and AGE-adducts, RAGE and VEGF in retinal pigment epithelial cells. Exp Eye Res. 2005;80(4):567–580. doi: 10.1016/j.exer.2004.11.009 15781285

42. Kernt M, Neubauer AS, Liegl R, Eibl KH, Alge CS, Lackerbauer CA, et al. Cytoprotective effects of a blue light-filtering intraocular lens on human retinal pigment epithelium by reducing phototoxic effects on vascular endothelial growth factor-alpha, Bax, and Bcl-2 expression. J Cataract Refract Surg. 2009;35(2):354–362. doi: 10.1016/j.jcrs.2008.10.052 19185255

43. Kernt M, Neubauer AS, Liegl RG, Hirneiss C, Alge CS, Wolf A, et al. Sorafenib prevents human retinal pigment epithelium cells from light-induced overexpression of VEGF, PDGF and PlGF. Br J Ophthalmol. 2010;94(11):1533–1539. doi: 10.1136/bjo.2010.182162 20962354

44. Cachafeiro M, Bemelmans AP, Samardzija M, Afanasieva T, Pournaras JA, Grimm C, et al. Hyperactivation of retina by light in mice leads to photoreceptor cell death mediated by VEGF and retinal pigment epithelium permeability. Cell Death Dis. 2013;4:e781. doi: 10.1038/cddis.2013.303 23990021

45. Arnault E, Barrau C, Nanteau C, Gondouin P, Bigot K, Vienot F, et al. Phototoxic action spectrum on a retinal pigment epithelium model of age-related macular degeneration exposed to sunlight normalized conditions. PLoS One. 2013;8(8):e71398. doi: 10.1371/journal.pone.0071398 24058402

46. Marie M, Bigot K, Angebault C, Barrau C, Gondouin P, Pagan D, et al. Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells. Cell Death Dis. 2018;9(3):287. doi: 10.1038/s41419-018-0331-5 29459695

47. Kim I, Ryan AM, Rohan R, Amano S, Agular S, Miller JW, et al. Constitutive expression of VEGF, VEGFR-1, and VEGFR-2 in normal eyes. Invest Ophthalmol Vis Sci. 1999;40(9):2115–2121. 10440268

48. Zhang J, Bai Y, Huang L, Qi Y, Zhang Q, Li S, et al. Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration. Cell Death Dis. 2015;6:e1972. doi: 10.1038/cddis.2015.330 26561782

49. Froger N, Matonti F, Roubeix C, Forster V, Ivkovic I, Brunel N, et al. VEGF is an autocrine/paracrine neuroprotective factor for injured retinal ganglion neurons. Scientific Reports. 2019;In press.

50. Saint-Geniez M, Maharaj AS, Walshe TE, Tucker BA, Sekiyama E, Kurihara T, et al. Endogenous VEGF is required for visual function: evidence for a survival role on muller cells and photoreceptors. PLoS One. 2008;3(11):e3554. doi: 10.1371/journal.pone.0003554 18978936

51. Endo A, Fukuhara S, Masuda M, Ohmori T, Mochizuki N. Selective inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2) identifies a central role for VEGFR-2 in human aortic endothelial cell responses to VEGF. J Recept Signal Transduct Res. 2003;23(2–3):239–254. doi: 10.1081/RRS-120025567 14626450

52. Whittles CE, Pocock TM, Wedge SR, Kendrew J, Hennequin LF, Harper SJ, et al. ZM323881, a novel inhibitor of vascular endothelial growth factor-receptor-2 tyrosine kinase activity. Microcirculation. 2002;9(6):513–522. doi: 10.1038/sj.mn.7800164 12483548

53. Akiyama H, Tanaka T, Doi H, Kanai H, Maeno T, Itakura H, et al. Visible light exposure induces VEGF gene expression through activation of retinoic acid receptor-alpha in retinoblastoma Y79 cells. Am J Physiol Cell Physiol. 2005;288(4):C913–920. doi: 10.1152/ajpcell.00116.2004 15613498

54. Atienzar-Aroca S, Flores-Bellver M, Serrano-Heras G, Martinez-Gil N, Barcia JM, Aparicio S, et al. Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells. J Cell Mol Med. 2016;20(8):1457–1466. doi: 10.1111/jcmm.12834 26999719

55. Marazita MC, Dugour A, Marquioni-Ramella MD, Figueroa JM, Suburo AM. Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for Age-related Macular Degeneration. Redox Biol. 2016;7:78–87. doi: 10.1016/j.redox.2015.11.011 26654980

56. Marie M. IOVS. 2015;56:ARVO E-Abstract 4256.

57. Murphy MP. Modulating mitochondrial intracellular location as a redox signal. Sci Signal. 2012;5(242):pe39. doi: 10.1126/scisignal.2003386 22990116

58. Yanagi Y, Inoue Y, Iriyama A, Jang WD. Effects of yellow intraocular lenses on light-induced upregulation of vascular endothelial growth factor. J Cataract Refract Surg. 2006;32(9):1540–1544. doi: 10.1016/j.jcrs.2006.04.012 16931269

59. Byeon SH, Lee SC, Choi SH, Lee HK, Lee JH, Chu YK, et al. Vascular endothelial growth factor as an autocrine survival factor for retinal pigment epithelial cells under oxidative stress via the VEGF-R2/PI3K/Akt. Invest Ophthalmol Vis Sci. 2010;51(2):1190–1197. doi: 10.1167/iovs.09-4144 19834034

60. Shih SC, Ju M, Liu N, Smith LE. Selective stimulation of VEGFR-1 prevents oxygen-induced retinal vascular degeneration in retinopathy of prematurity. J Clin Invest. 2003;112(1):50–57. doi: 10.1172/JCI17808 12840058

61. Rahimi N. Vascular endothelial growth factor receptors: molecular mechanisms of activation and therapeutic potentials. Exp Eye Res. 2006;83(5):1005–1016. doi: 10.1016/j.exer.2006.03.019 16713597

62. Rahimi N. VEGFR-1 and VEGFR-2: two non-identical twins with a unique physiognomy. Front Biosci. 2006;11:818–829. doi: 10.2741/1839 16146773

63. Ferrari G, Pintucci G, Seghezzi G, Hyman K, Galloway AC, Mignatti P. VEGF, a prosurvival factor, acts in concert with TGF-beta1 to induce endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2006;103(46):17260–17265. doi: 10.1073/pnas.0605556103 17088559

64. Ferrari G, Cook BD, Terushkin V, Pintucci G, Mignatti P. Transforming growth factor-beta 1 (TGF-beta1) induces angiogenesis through vascular endothelial growth factor (VEGF)-mediated apoptosis. J Cell Physiol. 2009;219(2):449–458. doi: 10.1002/jcp.21706 19180561


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