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Vitamin E succinate inhibits proliferation and migration of retinal pigment epithelial cells in vitro: therapeutic implication for proliferative vitreoretinopathy

  • Laboratory Investigation
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Abstract

• Background

Retinal pigment epithelial (RPE) cells play an important role in proliferative vitreoretinopathy (PVR). Vitamin E succinate is an ester form of a potent biological antioxidant, vitamin E, and has unique effects on various cells. We examined the effect of vitamin E succinate on proliferation and migration of cultured bovine RPE cells, since these are critical steps in the development of PVR.

• Methods

Bovine RPE cells were cultured in minimal essential medium (MEM) containing 10% fetal calf serum (MEM-10). Cells were incubated with MEM-10 containing 25 μM vitamin E, vitamin E succinate, butylated hydroxytoluene BHT) or d-mannitol. Cell proliferation was assessed by counting cell numbers on days 2, 4 and 6. 3H-Thymidine uptake was also examined in RPE cells incubated with various forms of vitamin E — vitamin E, vitamin E succinate, Trolox, γ-tocopherol, vitamin E acetate, vitamin E phosphate, vitamin E nicotinate — or antioxidants — BHT or d-mannitol (25 μM each). RPE cell migration was studied as follows: small area (5×15 mm) of confluent cultured RPE cells was denuded using a straight razor blade and incubation was continued for 20 h with MEM-10 containing vitamin E, vitamin E succinate, γ-tocopherol or BHT. The number of cells that migrated into the denuded area from the wound edge in each microscopic field (×20) was counted and expressed as a percentage of control (MEM-10 alone).

• Results

The antioxidants, vitamin E and BHT, stimulated RPE cell proliferation and 3H-thymidine incorporation compared with the control, while vitamin E succinate significantly inhibited both proliferation and 3H-thymidine uptake (IC50, 23 μM Other forms of vitamin E or d-mannitol had no effect. Neither vitamin E nor BHT had a significant effect on RPE cell migration (108.2% and 112.6% of control, respectively), but vitamin E succinate inhibited migration (58.3%). Cell viability, assessed by the trypan blue dye exclusion test, was not impaired by a 3-day incubation with 50 μM of vitamin E succinate.

• Conclusions

An ester form of a physiological antioxidant, vitamin E succinate, inhibits RPE cell proliferation and migration without causing cellular toxicity. These findings suggest its therapeutic potential for the pharmacological treatment of PVR.

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References

  1. Bascoboinik D, Szewczyk A, Hensey C, Azzi A (1991) Inhibition of cell proliferation by α-tocopherol. Role of protein kinase C. J Biol Chem 266:6188–6194

    Google Scholar 

  2. Bieri JG, Evarts RP (1974) Vitamin E activity of γ-tocopherol in the rat, chick and hamster. J Nutr 104:850–857

    Google Scholar 

  3. Blumenkranz MS, Hartzer MK (1994). The mechanism of action of drugs for the treatment of vitreoretinal scarring. In Ryan SJ (ed) Retina, vol 3. Mosby, St. Louis, pp 2281–2291

    Google Scholar 

  4. Borek C, Ong A, Mason H, Donahue L, Biaglow JE (1986) Selenium and vitamin E inhibit radiologenic and chemically induced transformation in vitro via different mechanisms. Proc Natl Acad Sci USA 83:1490–1494

    Google Scholar 

  5. Clark VM (1986) The cell biology of the retinal pigment epithelium. In: Adler R, Farber D (eds) The retina: II. Academic Press, Orlando, Fla, pp 129–168

    Google Scholar 

  6. Cunha-Vaz JG, Shakib M, Ashton N (1966) Studies on the permeability of the blood-retinal barrier. I. On the existence, development, and site of a blood-retinal barrier. Br J Ophthalmol 50:441–453

    Google Scholar 

  7. Dormandy TL (1978) Free-radical oxidation and antioxidants. Lancet 1:647–650

    Google Scholar 

  8. Fariss MW (1991) Oxygen toxicity: unique cytoprotective properties of vitamin E succinate in hepatocytes. Free Radic Biol Med 9:333–343

    Google Scholar 

  9. Gabrielian K, Osusky R, Sippy BD, Ryan SJ, Hinton DR (1994) The effect of TGF-β on interferon-γ induced HLA-DR expression in human RPE cells. Invest Ophthalmol Vis Sci 35:4253–4259

    Google Scholar 

  10. Glaser BM (1994) Surgery for proliferative vitreoretinopathy. In: Ryan SJ (ed) Retina, vol 3. Mosby, St. Louis, pp 2265–2280

    Google Scholar 

  11. Glaser BM, Lemor M (1994) Pathobiology of proliferative vitreoretinopathy. In: Ryan SJ (ed) Retina, vol 3. Mosby, St. Louis, pp 2249–2263

    Google Scholar 

  12. Gopalakrishna R, Anderson WB (1989) Ca2+ and phospholipid-independent activation of protein kinase C by selective oxidative modification of the regulatory domain. Proc Natl Acad Sci USA 86:6758–6762

    Google Scholar 

  13. Kim RS, Zaborniak CLF, Begleiter A, LaBella FS (1992) Antiproliferative properties of aminosteroid antioxidants on cultured cancer cells. Cancer Lett 64:61–66

    Google Scholar 

  14. Kline K, (1990) Sanders BG Jacobs MM (ed), Vitamins and minerals in the prevention of and treatment of cancer. CRC Press, Boca Raton, Fla, pp 189–205

    Google Scholar 

  15. Kunisaki M, Umeda F, Inoguchi T, Nawata H (1992) Vitamin E binds to specific binding sites and enhances prostacyclin production by cultured aortic endothelial cells Thromb Haemost 68:744–751

    Google Scholar 

  16. Murphy TL, Sakamoto T, Spee C, Gundimeda U, Soriano D, Gopalakrishna R, Hinton DR, Ryan SJ (1995) Migration of retinal pigment cells in vitro is regulated by protein kinase C. Exp Eye Res 60:683–695

    Google Scholar 

  17. Orlidge A, D'Amore PA (1987) Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. J Cell Biol 105:1455–1462

    Google Scholar 

  18. Pascoe GA, Olafsdottir K, Reed DJ (1987) Vitamin E protection against chemical-induced cell injury. 1. Maintenance of cellular protein thiols as a cytoprotective mechanism. Arch Biochem Biophys 256:150–158

    Google Scholar 

  19. Pentland AP, Morrison AR, Jacobs SC, Hruza LL, Hebert JS, Packer L (1992) Tocopherol analogs suppress arachidonic acid metabolism via phospholipase inhibition. J Biol Chem 267:15578–15584

    Google Scholar 

  20. Prasad KN, Edwards-Prasad J (1992) Vitamin E and cancer prevention: recent advances and future potentials. J Am Coll Nutr 11:487–500

    Google Scholar 

  21. Prasad KN, Ramanujam S, Gaudreau D (1979) Vitamin E induces morphological differentiation and increases the effect of ionizing radiation on neuroblastoma cells in culture. Proc Soc Exp Biol Med 161:570–573

    Google Scholar 

  22. Prasad KN, Cohrs RJ, Sharma OK (1990) Decreased expression of c-myc and H-ras oncogenes in vitamin E succinate induced morphologically differentiated murine B-16 melanoma cells in culture. Biochem Cell Biol 68:1250–1255

    Google Scholar 

  23. Reddanna P, Rao MK, Reddy CC (1985) Inhibition of 5-lipoxygenase by vitamin E. FEBS Lett 193:39–43

    Google Scholar 

  24. Retina Society Terminology Committee (1983) The classification of retinal detachment with proliferative vitreoretinopathy. Ophthalmology 90:121–125

    Google Scholar 

  25. Sahu SN, Edwards-Prasad J, Prasad KN (1988) Effect of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture. J Am Coll Nutr 7:285–293

    Google Scholar 

  26. Sakagami H, Asaka K, Abe E, Miyaura C, Suda T Kanno K (1981) Effect of DL-α tocopherol (vitamin E) on the differentiation of mouse myeloid leukemia cell. J Nutr Sci Vitaminol 27:291–300

    Google Scholar 

  27. Sakamoto T, Hinton DR, Sakamoto H, Oganesian A, Kohen L, Gopalakrishna R, Ryan SJ (1994) Collagen gel contraction induced by bovine retinal pigment epithelial cells and choroidal fibroblasts involves the protein kinase C pathway. Curr Eye Res 13:451–459

    Google Scholar 

  28. Sakamoto T, Sakamoto H, Sheu SJ, Gabrielian K, Ryan SJ, Hinton DR (1994) Intercellular gap formation of confluently cultured bovine retinal pigment epithelial cells induced by thrombin. Invest Ophthalmol Vis Sci 35:721–730

    Google Scholar 

  29. Sakamoto T, Ishibashi T, Kimura H, Yoshikawa H, Spee C, Harris MS, Hinton DR, Ryan SJ (1995) Effect of tecogalan sodium on angiogenesis in vitro by choroidal endothelial cells. Invest Ophthalmol Vis Sci 36:1076–1083

    Google Scholar 

  30. Scott ML (1980) Advances in our understanding of vitamin E. Fed Proc 39:2736–2739

    Google Scholar 

  31. Slack R, Proulx P (1989) Studies on the effects of vitamin E on neuroblastoma NIE 115. Nutr Cancer 12:75–82

    Google Scholar 

  32. Tappel AL (1972) Vitamin E and free radical peroxidation of lipids. Ann NY Acad Sci 203:12–28

    Google Scholar 

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Authors and Affiliations

  1. Doheny Eye Institute, 1450 San Pablo Street, 90033, Los Angeles, CA, USA

    Taiji Sakamoto, Hideya Kimura, Christine Spee & Stephen J. Ryan

  2. Department of Ophthalmology, University of Southern California, School of Medicine, Los Angeles, California

    Taiji Sakamoto, Hideya Kimura, Christine Spee & Stephen J. Ryan

  3. Department of Pathology, University of Southern California, School of Medicine, Los Angeles, California

    David R. Hinton

  4. Department of Cell and Neurobiology, University of Southern California, School of Medicine, Los Angeles, California

    Rayudu Gopalakrishna

Authors
  1. Taiji Sakamoto
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  2. David R. Hinton
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  3. Hideya Kimura
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  4. Christine Spee
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  5. Rayudu Gopalakrishna
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  6. Stephen J. Ryan
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Sakamoto, T., Hinton, D.R., Kimura, H. et al. Vitamin E succinate inhibits proliferation and migration of retinal pigment epithelial cells in vitro: therapeutic implication for proliferative vitreoretinopathy. Graefe's Arch Clin Exp Ophthalmol 234, 186–192 (1996). https://doi.org/10.1007/BF00462031

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  • DOI: https://doi.org/10.1007/BF00462031

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