Résumés
Résumé
Les maladies de la rétine sont la première cause de cécité. Les possibilités de traitement sont limitées du fait de la difficulté d’accès à ce tissu, prolongement du système nerveux central tapissant l’intérieur du globe oculaire. Toute stratégie thérapeutique dans le domaine des maladies de la rétine doit comporter une méthode de délivrance de l’agent thérapeutique in situ. Les recherches portant sur les méthodes de délivrance des produits actifs sont de ce fait en plein essor. Elles sont au carrefour de la pharmacologie, de la pharmacotechnie, des biomatériaux, de l’ophtalmologie et de la biologie. Des dispositifs solides, biodégradables ou non, peuvent être implantés dans la cavité vitréenne et des polymères biodégradables peuvent y être injectés. Des méthodes non invasives comme l’iontophorèse ou le transport trans-scléral sont en cours de développement. Les premières applications de ces procédés ont récemment vu le jour en clinique humaine. L’intensification des recherches dans le domaine du transfert intra-oculaire de médicaments indique que de véritables perspectives vont s’ouvrir pour le traitement des maladies rétiniennes.
Summary
Retinal diseases are nowadays the most common causes of vision threatening in developed countries. Therapeutic advances in this field are hindered by the difficulty to deliver drugs to the posterior segment of the eye. Due to anatomical barriers, the ocular biodisponibility of systemically administered drugs remains poor, and topical instillation is not adequate to achieve therapeutic concentrations of drugs in the back of the eye. Ocular drug delivery has thus become one of the main challenges of modern ophthalmology. A multidisciplinary research is being conducted worldwide including pharmacology, biomaterials, ophthalmology, pharmaceutics, and biology. New promising fields have been developed such as implantable or injectable slow release intravitreal devices and degradable polymers, dispersed polymeric systems for intraocular drug delivery, and transscleral delivery devices such as iontophoresis, osmotic pumps or intra-scleraly implantable materials. The first clinical applications emerging from this research are now taking place, opening new avenues for the treatment of retinal diseases.
Parties annexes
Références
- 1. Reichel E, Berrocal A, Ip M, et al. Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration. Ophthalmology 1999 ; 106 : 1908-14.
- 2. Schmidt-Refurth U, Miller J, Sickenberg M, et al. Photodynamic therapy with verteprofin for choroidal neovascularization cauzed by age-related macular degeneration. Arch Ophthalmol 1999 ; 117 : 1177-87.
- 3. Hauswirth WW, Lewin AS. Ribozyme uses in retinal gene therapy. Prog Retin Eye Res 2000 ; 19 : 689-710.
- 4. Acland GM, Aguire GD, Ray J, et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 2001 ; 28 : 92-5.
- 5. Liang FQ, Dejneka NS, Cohen DR, et al. Aav-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse. Mol Ther 2001 ; 3 : 241-8.
- 6. Ferrara N, Alitalo K. Clinical applications of angiogenic growth factors and their inhibitors. Nature Med 1999 ; 5 : 1359-64.
- 7. Nir I, Kedzierski W, Chen J, Travis GH. Expression of Bcl-2 protects against photoreceptor degeneration in retinal degeneration slow (rds) mice. J Neurosci 2000 ; 15 : 2150-4.
- 8. Frasson M, Sahel JA, Fabre M, et al. Retinitis pigmentosa : Rod photoreceptor rescue by a calcium-channel blocker in the rd mouse. Nature Med 1999 ; 5 : 1183-7.
- 9. Maurice D, Mishima S. Ocular pharmacokinetics in ML. In : Sears ML, ed. Pharmacology of the eye. Berlin : Springer-Verlag, 1984 : 19-116.
- 10. Tojo K, Isowaki A. Pharmacokinetic model for in vivo/in vitro correlation of intravitreal drug delivery. Advanced Drug Delivery Rev 2001 ; 52 : 17-24.
- 11. Weijtens O, van der Sluijs FA, Schoemaker RC, et al. Peribulbar corticosteroids injection : Vitreal and serum concentrations after dexamethasone disodium phosphate injection. Am J Ophthalmol 1997 ; 123 : 358-63.
- 12. Bodker FS, Ticho BH, Feist RM, Lam TT. Intraocular dexamethasone penetration via subconjunctival or retrobulbar injections in rabbits. Ophthalmic Surg 1993 ; 24 : 453-7.
- 13. Blair NP, Evans MA, Lesar TS, Zeimer RC. Fluorescein and fluorescein glucuronide pharmacokinetics after intravenous injection. Invest Ophthalmol Vis Sci 1986 ; 27 : 1107-14.
- 14. Araie M, Maurice DM. The loss of fluorescein, fluorescein glucuronide and fluorescein isothiocyanate dextran from the vitreous by the anterior and retinal pathways. Exp Eye Res 1991 ; 52 : 27-39.
- 15. Martin DF, Parks DJ, Mellow SD, et al. Treatment of CMV retinitis with an intraocular sustained-release ganciclovir implant : A randomized controlled clinical trial. Arch Ophthalmol 1994 ; 112 : 1531-9.
- 16. Jaffe G, Ben-Nun J, Guo H, et al. Fluocinolone acetonide sustained drug delivery device to treat severe uveitis. Ophthalmology 2000 ; 11 : 2024-33.
- 17. Kimura H, Ogura Y, Hashizoe M, et al. A new vitreal drug delivery system using an implantable biodegradable polymeric device. Invest Ophthalmol Vis Sci 1994 ; 35 : 2815-9.
- 18. Kunou N, Ogura Y, Yasukawa T, et al. Long term sustained release of GC from biodegradable scleral implant for the treatment of CMV retinitis. J Control Release 2000 ; 10 : 263-71.
- 19. Hashizoe M, Ogura Y, Takanashi T, et al. Implantable biodegradable polymeric device in the treatment of experimental proliferative vitreoretinopathy. Curr Eye Res 1995 ; 14 : 473-7.
- 20. Kunou N, Ogura Y, Honda Y, et al. Biodegradable scleral implant for controlled intraocular delivery of betamethasone phosphate . Int J Biomat Res 2000 ; 51 : 634-41.
- 21. Peyman GA, Yang D, Khoobehi B, et al. In vitro evaluation of polymeric matrix and porous biodegradable reservoir devices for slow-release drug delivery. Ophthalmic Surg and lasers 1996 ; 27 : 384-91.
- 22. Chasin M, Domb A, Ron E, et al. Polyanhydrides as drug delivery systems. In : Chasin M, Langer R, eds. Biodegradable polymers as drug delivery systems. New York : Marcel Dekker, 1990 : 43-70.
- 23. Heller J, Barr J, Shen H, et al. Poly(ortho esters)-their development and some recent applications. Eur J Pharm Biopharm 2000 ; 50 : 121-8.
- 24. Behar-Cohen F, BenEzra D, Einmahl S, Gurny R. Challenge of intraocular dug delivery. Eur J Pharm Rev 2001 ; 6 : 35-40.
- 25. Einmahl S, Capancioni S, Schwach-Abdellaoui K, et al. Therapeutic applications of viscous and injectable poly(ortho) esters. Adv Drug Deliv Rev 2001 ; 53 : 45-73.
- 26. Einmahl S, Behar-Cohen F, Tabatabay C, et al. A viscous bioerodible poly(ortho ester) as a new biomaterial for intraocular application. J Biomed Mater Res 2000 ; 5 : 566-73.
- 27. Einmahl S, Behar-Cohen F, D’Hermies F, et al. A new poly(ortho ester)-based drug delivery system for the adjunct treatment of filtering surgery. Invest Ophthalmol Vis Sci 2000 ; 42 : 695-700.
- 28. Einmahl S, Savoldelli M, D’Hermies F, et al. Evaluation of a new biomaterial in the suprachoroidal space. Invest Ophthalmol Vis Sci 2002 ; 43 : 1533-9.
- 29. Sakurai E, Ozeki H, Kunou N, Ogura Y. Effect of particle size of polymeric nanospheres on intravitreous kinetics. Ophthalmic Res 2001 ; 33 : 31-6.
- 30. Bourges JL , Gautier SE, Delie F, et al. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactides nanoparticles. Invest Ophthalmol Vis Sci 2003 ; 44 : 3562-9.
- 31. Peyman G, Convay M, Khoobei B, Soike K. Clearance of of microsphere-entrapped 5-FU and cytosine arabinoside from the vitreous of primate. Int Ophthalmol 1992 ; 16 : 109-13.
- 32. Moritera T, Ogura Y, Yoshimura N, et al. Biodegradable microspheres containing adriamycin in the treatment of proliferative vitreo retinopathy. Invest Ophthalmol Vis Sci 1992 ; 33 : 3125-30.
- 33. Akula SK, Ma PE, Peyman GA, et al. Treatment of cytomegalovirus retinitis with intravitreal injection of liposome encapsulated ganciclovir in a patient with AIDS. Br J Ophthalmol 1994 ; 78 : 677-80.
- 34. Bochot A, Fattal E, Boutet V, et al. Intravitreal delivery of oligonucleotides by sterically stabilized liposomes. Invest Ophthalmol Vis Sci 2002 ; 43 : 253-9.
- 35. Barza M, Stuart M, Szoka F, Jr. Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes. Invest Ophthalmol Vis Sci 1987 ; 28 : 893-900.
- 36. Ambati J, Canakis CS, Miller JW, et al. Diffusion of high molecular weight compounds through sclera. Invest Ophthalmol Vis Sci 2000 ; 41 : 1181-5.
- 37. Geroski DH, Edelhauser HF. Transscleral drug delivery for posterior segment disease. Adv Drug Deliv Rev 2001 ; 52 : 37-48.
- 38. Ambati J, Gragoudas ES, Miller JW, et al. Transscleral delivery of bioactive protein to the choroid and retina. Invest Ophthalmol Vis Sci 2000 ; 41 : 1186-91.
- 39. Behar-Cohen F, Parel JM, El Aouni A, Chauvaud D. Iontophoresis : The past and the future. J Fr Ophthalmol 2001 ; 24 : 319-27.
- 40. Voigt M, de Kozak Y, Halhal M, et al. Down regulation of NOSII gene expression by iontophoresis of anti-sense oligonucleotide in endotoxin-induced uveitis. Biochem Biophys Res Comm 2002 ; 295 : 336-41.
- 41. Lam TT, Fu J, Tso MO. A histopathological study of retinal lesions inflicted by transscleral iontophoresis Graefe’s Arch Clin Exp Ophthalmol 1991 ; 229 : 389-94.
- 42. Behar-Cohen FF, El Aouni A, Gautier S, et al. Transscleral coulomb-controlled iontophoresis of methylprednisolone into the rabbit eye : Influence of duration of treatment, current intensity and drug concentration in ocular tissues and fluids levels. Exp Eye Res 2002 ; 74 : 51-9.
- 43. Halhal M, Renard G, Courtois Y, et al. Iontophoresis from the lab to the bedside. Exp Eye Res 2004 ; 78 : 751-7.