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Polylactide-glycoli acid and rapamycin coating intraocular lens prevent posterior capsular opacification in rabbit eyes

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Abstract

Objectives

Posterior capsular opacification (PCO) is caused by the proliferation and migration of residual lens epithelium cells (LECs) after extracapsular cataract extraction (ECCE). Rapamcin (RAPA) is known to be a potent immunosuppressive drug with anti-inflammatory and anti-proliferative effects. The aim of this study was to investigate the safety and efficacy of rapamycin sustained release from modified intraocular lens (IOLs) in the prevention of PCO in rabbits.

Methods

Three types of IOLs were used, including the original IOL without modification, IOL with polylactide-glycoli acid (PLGA) coating (PLGA-IOL), and RAPA-loaded PLGA-IOL (RAPA-PLGA-IOL). Sixty New Zealand albino rabbits undergoing phacoemulsification in left eyes were randomly and equally divided into three groups. Group A was implanted with the original IOLs, group B was implanted with the PLGA-IOLs, and group C was implanted with the RAPA-PLGA-IOLs. All of the 60 treated left eyes were examined by a slit-lamp microscope. The concentrations of RAPA in the aqueous humor and blood were determined by high-performance liquid chromatography (HPLC), indicating an vivo release of drug from the polymer carrier. Anterior segment tissue was histologically examined, and wet posterior capsules were weighed. Six months after intervention the PCO was graded.

Results

The mean concentrations of RAPA in the aqueous humor from group C at 2 h, 1 days, 3 days, and 7 days after operation were 12.81 ± 1.27 μg/ml, 14.57 ± 0.99 μg/ml, 6.39 ± 0.95 μg/ml, and 1.10 ± 0.32 μg /ml respectively. The concentrations of RAPA in blood were undetectable. During the early days after the operation, the reactions of the anterior chamber from groups A and B were more severe than from group C. Our findings showed that the initial appearance of PCO in group C was much later than in the other two groups. The wet posterior capsules were weighed to be 0.3735 ± 0.0943 g (group A), 0.3754 ± 0.1093 g (group B), and 0.0432 ± 0.0089 g (group C). Histological observation showed a similar phenomenon, that there was remarkably less accumulation of lens materials on the posterior capsules in group C than in the other two groups.

Conclusion

Our findings suggest that the designed RAPA-PLGA-IOL effectively prevented formation and development of PCO for a relatively long duration.

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References

  1. Stark WJ, Sommer A, Smith RE (1989) Changing trends in intraocular lens implantation. Arch Ophthalmol 107:1441–1444

    PubMed  CAS  Google Scholar 

  2. Ohrloff C, Schalnus R, Rothe R, Spitznas M (1990) Role of the posterior capsule in the aqueous-vitreous barrier in aphakic and pseudophakic eyes. J Cataract Refract Surg 16:198–201

    PubMed  CAS  Google Scholar 

  3. McDonnell PJ, Patel A, Green WR (1985) Comparison of intracapsular and extracapsular cataract surgery. Histopathologic study of eyes obtained postmortem. Ophthalmology 92:1208–1225

    PubMed  CAS  Google Scholar 

  4. Schaumberg DA, Dana MR, Christen WG, Glynn RJ (1998) A systematic overview of the incidence of posterior capsule opacification. Ophthalmology 105:1213–1221. doi:10.1016/S0161-6420(98)97023-3

    Article  PubMed  CAS  Google Scholar 

  5. Apple DJ, Solomon KD, Tetz MR, Assia EI, Holland EY, Legler UF, Sai JC, Castaneda VE, Hoggatt JP, Kostick AM (1992) Posterior capsule opacification. Surv Ophthalmol 37:73–116. doi:10.1016/0039-6257(92)90073-3

    Article  PubMed  CAS  Google Scholar 

  6. Kappelhof JP, Vrensen GF (1992) The pathology of after-cataract. A minireview. Acta Ophthalmol Suppl 205:13–24

    PubMed  Google Scholar 

  7. Gao X, Cai KL, Wu XL, Yang XL, Huo W (2006) Rapamycin inhibits the pathogenesis of posterior capsule opacification experimental study on rabbit. J Shandong Univ 6:634–637

    Google Scholar 

  8. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE, SIRIUS Investigators (2003) Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 349:1315–1323. doi:10.1056/NEJMoa035071

    Article  PubMed  CAS  Google Scholar 

  9. Yang P, Li S (1998) Uveitis. People’s Medical Publishing House, Beijing

    Google Scholar 

  10. Hepsen IF, Bayramlar H, Gültek A, Özen S, Tilgen F, Evereklioglu C (1997) Caffeic acid phenethyl ester to inhibit posterior capsule opacification in rabbits. J Cataract Refract Surg 23:1572–1576

    PubMed  CAS  Google Scholar 

  11. Cobo LM, Ohsawa E, Chandler D, Arguello R, George G (1984) Pathogenesis of capsular opacification after extracapsular cataract extraction. An animal model. Ophthalmology 91:857–863

    PubMed  CAS  Google Scholar 

  12. Frezzotti R, Caporossi A (1990) Pathogenesis of posterior capsule opacification. I. Epidemiological and clinicostatistical data. J Cataract Refract Surg 16:347–352

    PubMed  CAS  Google Scholar 

  13. Frezzotti R, Caporossi A, Mastrengelo D, Hadjistilianou T, Tosi P, Cintorino M, Minacci C (1990) Pathogenesis of posterior capsule opacification. II. Histopathological and in vitro culture findings. J Cataract Refract Surg 16:353–360

    PubMed  CAS  Google Scholar 

  14. Green WR, McDonnell PJ (1985) Opacification of the posterior capsule. Trans Ophthalmol Soc U K 104:727–739

    PubMed  Google Scholar 

  15. McDonnell PJ, Stark WJ, Green WR (1984) Posterior capsule opacification: a specular microscopic study. Ophthalmology 91:853–856

    PubMed  CAS  Google Scholar 

  16. McDonnell PJ, Krause W, Glaser BM (1988) In vitro inhibition of lens epithelial cell proliferation and migration. Ophthalmic Surg 19:25–30

    PubMed  CAS  Google Scholar 

  17. Hansen TJ, Tyndall R, Soll DB (1987) Methotrexate-anticollagen conjugate inhibits in vitro lens cell outgrowth. Invest Ophthalmol Vis Sci 28:1206–1209

    PubMed  CAS  Google Scholar 

  18. Sehgal SN, Baker H, Vézina C (1975) Rapamycin (AY-22,989), A new antifungal antibiotic: II. Fermentation, isolation, and characterization. J Antibiot 28:727–732

    PubMed  CAS  Google Scholar 

  19. Vézina C, Kudelski A, Sehgal SN (1975) Rapamycin (AY-22,989). A new antifungal antibiotic: I. Toxonomy of the producing streptomycete and isolation of the active principle. J Antibiot 28:721–726

    PubMed  Google Scholar 

  20. Suzuki T, Kopia G, Hayashi S, Bailey LR, Llanos G, Wilensky R, Klugherz BD, Papandreou G, Narayan P, Leon MB, Yeung AC, Tio F, Tsao PS, Falotico R, Carter AJ (2001) Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model. Circulation 104:1188–1193. doi:10.1161/hc3601.093987

    Article  PubMed  CAS  Google Scholar 

  21. Gummert JF, Ikonen T, Morris RE (1999) Newer immunosuppressive drugs: a review. J Am Soc Nephrol 10:1366–1380

    PubMed  CAS  Google Scholar 

  22. Marx SO, Jayaraman T, Go LO, Marks AR (1995) Rapamycin-FKBP inhibits cell cycle regulators of proliferation in vascular smooth muscle cells. Circ Res 76:412–417

    PubMed  CAS  Google Scholar 

  23. Zhao J, Cai KL (2007) Effects of rapamycin on regeneration of cultured rabbit lens epithelial cells. Chin J Optom Ophthalmol 9:37–39

    CAS  Google Scholar 

  24. Regar E, Sianos G, Serruys PW (2001) Stent development and local drug delivery. Br Med Bull 59:227–248. doi:10.1093/bmb/59.1.227

    Article  PubMed  CAS  Google Scholar 

  25. Klingemann HG (1995) Update on immunosuppressive drugs (A report from the International Consensus Conference on Immunosuppressive Drugs). DN&P 8:303–309

    Google Scholar 

  26. Ohia EO, Mancino M, Kulkarni PS (1992) Effects of steroids and immunosuppressive drug on endotoxin-uveitis in rabbits. J Ocul Pharmacol 8:295–307

    Article  PubMed  CAS  Google Scholar 

  27. Nishi O, Nishi K, Imanishi M, Tada Y, Shirasawa E (1995) Effect of the cytokines on the prostaglandin E2 synthesis by lens epithelial cells of human cataracts. Br J Ophthalmol 79:934–938. doi:10.1136/bjo.79.10.934

    Article  PubMed  CAS  Google Scholar 

  28. Roberge FG, Xu D, Chan CC, de Smet MD, Nussenblatt RB, Chen H (1993) Treatment of autoimmune uveoretinitis in the rat with rapamycin, an inhibitor of lymphocyte growth factor signal transduction. Curr Eye Res 12:197–203. doi:10.3109/02713689308999487

    Article  PubMed  CAS  Google Scholar 

  29. Dejneka NS, Kuroki AM, Fosnot J, Tang W, Tolentino MJ, Bennett J (2004) Systemic rapamycin inhibits retinal and choroidal neovascularization in mice. Mol Vis 10:964–972

    PubMed  CAS  Google Scholar 

  30. Chan CC, Martin DF, Xu D, Roberge FG (1995) Side effects of rapamycin in the rat. J Ocul Pharmacol Ther 11:177–181

    Article  PubMed  CAS  Google Scholar 

  31. Buech G, Bertelmann E, Pleyer U, Siebenbrodt I, Borchert HH (2007) Formulation of sirolimus eye drops and corneal permeation studies. J Ocul Pharmacol Ther 23:292–303. doi:10.1089/jop.2006.130

    Article  PubMed  CAS  Google Scholar 

  32. Yasukawa T, Kimura H, Tabata Y, Miyamoto H, Honda Y, Ogura Y (2002) Sustained release of cis-hydroxyproline in the treatment of experimental proliferative vitreoretinopathy in rabbits. Graefes Arch Clin Exp Ophthalmol 240:672–678. doi:10.1007/s00417-002-0484-9

    Article  PubMed  CAS  Google Scholar 

  33. Nishi O, Nishi K, Yamada Y, Mizumoto Y (1995) Effect of indomethacin-coated posterior chamber intraocular lenses on postoperative inflammation and posterior capsule opacification. J Cataract Refract Surg 21:574–578

    PubMed  CAS  Google Scholar 

  34. Kwon YS, Kim JC (2006) Inhibition of corneal neovascularization by rapamycin. Exp Mol Med 38:173–179

    PubMed  CAS  Google Scholar 

  35. Shi W, Gao H, Xie L, Wang S (2006) Sustained intraocular rapamycin delivery effectively prevents high-risk corneal allograft rejection and neovascularization in rabbits. Invest Ophthalmol Vis Sci 47:3339–3344. doi:10.1167/iovs.05-1425

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a grant from the National Natural Science Foundation and the National High Technology Research and Development Program of China (NSFC: 30870622) (863: 2007AA02Z450). We thank Xiaoying CUI, Jinzhu WU, and Weiqi GAO for the English revision.

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Authors and Affiliations

  1. Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Str, Nangang District, Harbin, Heilongjiang Province, 150001, People’s Republic of China

    Hongling Liu, Lan Wu, Shaoying Fu, Yongsheng Hou, Ping Liu, Hao Cui, Jingjing Liu, Lin Xing & Xiaomei Zhang

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  1. Hongling Liu
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Correspondence to Xiaomei Zhang.

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Liu, H., Wu, L., Fu, S. et al. Polylactide-glycoli acid and rapamycin coating intraocular lens prevent posterior capsular opacification in rabbit eyes. Graefes Arch Clin Exp Ophthalmol 247, 801–807 (2009). https://doi.org/10.1007/s00417-008-1007-0

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  • DOI: https://doi.org/10.1007/s00417-008-1007-0

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