Barriers to transscleral drug delivery to the retina

Ocular Drug Delivery Systems: Barriers and Application of Nanoparticulate Systems

Volumn , Issue , 2012, Pages 133-156

  Almazan, Alexandra ^a   Lee, Susan S ^a   Ross, Aron D ^b   Robinson, Michael R ^a  

^a ALLERGAN INC   (United States)

^b Triton Biomedical Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84979072907     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/b12950     Document Type: Chapter

References (147)

1. Raghava S, Hammond M, Kompella UB. Periocular routes for retinal drug delivery. Expert Opin Drug Deliv. 2004;1(1):99-114.
2. Geroski DH, Edelhauser HF. Drug delivery for posterior segment eye disease. Invest Ophthalmol Vis Sci. 2000;41(5):961-964.
3. Hughes PM, Olejnik O, Chang-Lin JE, Wilson CG. Topical and systemic drug delivery to the posterior segments. Adv Drug Deliv Rev. 2005;57(14):2010-2032.
4. Ciulla TA, Walker JD, Fong DS, Criswell MH. Corticosteroids in posterior segment dis-ease: An update on new delivery systems and new indications. Curr Opin Ophthalmol. 2004;15(3):211-220.
5. Smith CL. Local therapy for cytomegalovirus retinitis. Ann Pharmacother. 1998;32(2): 248-255.
6. Kralinger MT, Kieselbach GF, Voigt M et al. Experimental model for proliferative vitreoretinopathy by intravitreal dispase: Limited by zonulolysis and cataract. Ophthalmologica. 2006;220(4):211-216.
7. Ozkiris A, Erkilic K. Complications of intravitreal injection of triamcinolone acetonide. Can J Ophthalmol. 2005;40(1):63-68.
8. Nicolo M, Ghiglione D, Calabria G. Retinal pigment epithelial tear following intravit-real injection of bevacizumab (Avastin). Eur J Ophthalmol. 2006;16(5):770-773.
9. Shah CP, Hsu J, Garg SJ, Fischer DH, Kaiser R. Retinal pigment epithelial tear after intravitreal bevacizumab injection. Am J Ophthalmol. 2006;142(6):1070-1072.
10. Sutter FK, Gillies MC. Pseudo-endophthalmitis after intravitreal injection of triamcino-lone. Br J Ophthalmol. 2003;87(8):972-974.
11. Nelson ML, Tennant MT, Sivalingam A, Regillo CD, Belmont JB, Martidis A. Infectious and presumed noninfectious endophthalmitis after intravitreal triamcinolone acetonide injection. Retina. 2003;23(5):686-691.
12. Roth DB, Chieh J, Spirn MJ, Green SN, Yarian DL, Chaudhry NA. Noninfectious endophthalmitis associated with intravitreal triamcinolone injection. Arch Ophthalmol. 2003;121(9):1279-1282.
13. Blatsios G, Tzimas AS, Mattheolabakis G, Panagi Z, Avgoustakis K, Gartaganis SP. Development of biodegradable controlled release scleral systems of triamcinolone ace-tonide. Curr Eye Res. 2010;35(10):916-924.
14. Bonini-Filho MA, Jorge R, Barbosa JC, Calucci D, Cardillo JA, Costa RA. Intravitreal injection versus sub-Tenon’s infusion of triamcinolone acetonide for refractory diabetic macular edema: A randomized clinical trial. Invest Ophthalmol Vis Sci. 2005;46(10):3845-3849.
15. Ohguro N, Okada AA, Tano Y. Trans-Tenon’s retrobulbar triamcinolone infusion for diffuse diabetic macular edema. Graefes Arch Clin Exp Ophthalmol. 2004;242(5): 444-445.
16. Okada AA, Wakabayashi T, Kojima E, Asano Y, Hida T. Trans-Tenon’s retrobul-bar triamcinolone infusion for small choroidal neovascularisation. Br J Ophthalmol. 2004;88(8):1097-1098.
17. Okada AA, Wakabayashi T, Morimura Y et al. Trans-Tenon’s retrobulbar triamcinolone infusion for the treatment of uveitis. Br J Ophthalmol. 2003;87(8):968-971.
18. Ayalasomayajula SP, Kompella UB. Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur J Pharmacol. 2005;511(2-3):191-198.
19. Cheruvu NP, Amrite AC, Kompella UB. Effect of eye pigmentation on transscleral drug delivery. Invest Ophthalmol Vis Sci. 2008;49(1):333-341.
20. Kompella UB, Bandi N, Ayalasomayajula SP. Subconjunctival nano- and microparti-cles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci. 2003;44(3):1192-1201.
21. Gilbert JA, Simpson AE, Rudnick DE, Geroski DH, Aaberg TM, Jr., Edelhauser HF. Transscleral permeability and intraocular concentrations of cisplatin from a collagen matrix. J Control Release. 2003;89(3):409-417.
22. Zignani M, Einmahl S, Baeyens V et al. A poly(ortho ester) designed for combined ocu-lar delivery of dexamethasone sodium phosphate and 5-fluorouracil: Subconjunctival tolerance and in vitro release. Eur J Pharm Biopharm. 2000;50(2):251-255.
23. Wang G, Tucker IG, Roberts MS, Hirst LW. In vitro and in vivo evaluation in rabbits of a controlled release 5-fluorouracil subconjunctival implant based on poly(D, L-lactide-co-glycolide). Pharm Res. 1996;13(7):1059-1064.
24. Kato A, Kimura H, Okabe K, Okabe J, Kunou N, Ogura Y. Feasibility of drug delivery to the posterior pole of the rabbit eye with an episcleral implant. Invest Ophthalmol Vis Sci. 2004;45(1):238-244.
25. Okabe K, Kimura H, Okabe J, Kato A, Kunou N, Ogura Y. Intraocular tissue distribution of betamethasone after intrascleral administration using a non-biodegradable sustained drug delivery device. Invest Ophthalmol Vis Sci. 2003;44(6):2702-2707.
26. Okabe J, Kimura H, Kunou N, Okabe K, Kato A, Ogura Y. Biodegradable intra-scleral implant for sustained intraocular delivery of betamethasone phosphate. Invest Ophthalmol Vis Sci. 2003;44(2):740-744.
27. Ambati J, Gragoudas ES, Miller JW et al. Transscleral delivery of bioactive protein to the choroid and retina. Invest Ophthalmol Vis Sci. 2000;41(5):1186-1191.
28. Okabe K, Kimura H, Okabe J et al. Effect of benzalkonium chloride on transscleral drug delivery. Invest Ophthalmol Vis Sci. 2005;46(2):703-708.
29. Eljarrat-Binstock E, Pe’er J, Domb AJ. New techniques for drug delivery to the posterior eye segment. Pharm Res. 2010;27(4):530-543.
30. Molokhia SA, Jeong EK, Higuchi WI, Li SK. Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI. Exp Eye Res. 2009;88(3):418-425.
31. Cardillo JA, Melo LA, Jr., Costa RA et al. Comparison of intravitreal versus posterior sub-Tenon’s capsule injection of triamcinolone acetonide for diffuse diabetic macular edema. Ophthalmology. 2005;112(9):1557-1563.
32. Lee TW, Robinson JR. Drug delivery to the posterior segment of the eye III: The effect of parallel elimination pathway on the vitreous drug level after subconjunctival injec-tion. J Ocul Pharmacol Ther. 2004;20(1):55-64.
33. Ambati J, Adamis AP. Transscleral drug delivery to the retina and choroid. Prog Retin Eye Res. 2002;21(2):145-151.
34. Boubriak OA, Urban JP, Akhtar S, Meek KM, Bron AJ. The effect of hydration and matrix composition on solute diffusion in rabbit sclera. Exp Eye Res. 2000;71(5): 503-514.
35. Hamalainen KM, Kananen K, Auriola S, Kontturi K, Urtti A. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci. 1997;38(3):627-634.
36. Kao JC, Geroski DH, Edelhauser HF. Transscleral permeability of fluorescent-labeled antibiotics. J Ocul Pharmacol Ther. 2005;21(1):1-10.
37. Shuler RK, Jr., Dioguardi PK, Henjy C, Nickerson JM, Cruysberg LP, Edelhauser HF. Scleral permeability of a small, single-stranded oligonucleotide. J Ocul Pharmacol Ther. 2004;20(2):159-168.
38. Cruysberg LP, Franklin AJ, Sanders J et al. Effective transscleral delivery of two reti-nal anti-angiogenic molecules: Carboxyamido-triazole (CAI) and 2-methoxyestradiol (2ME2). Retina. 2005;25(8):1022-1031.
39. Cheruvu NP, Kompella UB. Bovine and porcine transscleral solute transport: Influence of lipophilicity and the choroid-Bruch’s layer. Invest Ophthalmol Vis Sci. 2006;47(10):4513-4522.
40. Cruysberg LP, Nuijts RM, Geroski DH, Koole LH, Hendrikse F, Edelhauser HF. In vitro human scleral permeability of fluorescein, dexamethasone-fluorescein, meth-otrexate-fluorescein and rhodamine 6G and the use of a coated coil as a new drug delivery system. J Ocul Pharmacol Ther. 2002;18(6):559-569.
41. Prausnitz MR, Noonan JS. Permeability of cornea, sclera, and conjunctiva: A literature analysis for drug delivery to the eye. J Pharm Sci. 1998;87(12):1479-1488.
42. Ambati J, Canakis CS, Miller JW et al. Diffusion of high molecular weight compounds through sclera. Invest Ophthalmol Vis Sci. 2000;41(5):1181-1185.
43. Ahmed I, Gokhale RD, Shah MV, Patton TF. Physicochemical determinants of drug dif-fusion across the conjunctiva, sclera, and cornea. J Pharm Sci. 1987;76(8):583-586.
44. Edwards A, Prausnitz MR. Fiber matrix model of sclera and corneal stroma for drug delivery to the eye. AIChE. 1998;44(1):214-225.
45. Boubriak OA, Urban JP, Bron AJ. Differential effects of aging on transport properties of anterior and posterior human sclera. Exp Eye Res. 2003;76(6):701-713.
46. Curtin BJ. Physiopathologic aspects of scleral stress-strain. Trans Am Ophthalmol Soc. 1969;67:417-461.
47. Jiang J, Geroski DH, Edelhauser HF, Prausnitz MR. Measurement and prediction of lat-eral diffusion within human sclera. Invest Ophthalmol Vis Sci. 2006;47(7):3011-3016.
48. Kansara V, Mitra AK. Evaluation of an ex vivo model implication for carrier-mediated retinal drug delivery. Curr Eye Res. 2006;31(5):415-426.
49. Maurice DM, Polgar J. Diffusion across the sclera. Exp Eye Res. 1977;25(6):577-582.
50. Dunlevy JR, Rada JA. Interaction of lumican with aggrecan in the aging human sclera. Invest Ophthalmol Vis Sci. 2004;45(11):3849-3856.
51. Lee SB, Geroski DH, Prausnitz MR, Edelhauser HF. Drug delivery through the sclera: Effects of thickness, hydration, and sustained release systems. Exp Eye Res. 2004;78(3):599-607.
52. Olsen TW, Edelhauser HF, Lim JI, Geroski DH. Human scleral permeability: Effects of age, cryotherapy, transscleral diode laser, and surgical thinning. Invest Ophthalmol Vis Sci. 1995;36(9):1893-1903.
53. Cruysberg LP, Nuijts RM, Geroski DH, Gilbert JA, Hendrikse F, Edelhauser HF. The influence of intraocular pressure on the transscleral diffusion of high-molecular-weight compounds. Invest Ophthalmol Vis Sci. 2005;46(10):3790-3794.
54. Rudnick DE, Noonan JS, Geroski DH, Prausnitz MR, Edelhauser HF. The effect of intraocular pressure on human and rabbit scleral permeability. Invest Ophthalmol Vis Sci. 1999;40(12):3054-3058.
55. Moore DJ, Hussain AA, Marshall J. Age-related variation in the hydraulic conductivity of Bruch’s membrane. Invest Ophthalmol Vis Sci. 1995;36(7):1290-1297.
56. Amaral J, Fariss RN, Campos MM et al. Transscleral-RPE permeability of PEDF and ovalbumin proteins: Implications for subconjunctival protein delivery. Invest Ophthalmol Vis Sci. 2005;46(12):4383-4392.
57. Pitkänen L, Ranta VP, Moilanen H, Urtti A. Permeability of retinal pigment epithe-lium: Effects of permeant molecular weight and lipophilicity. Invest Ophthalmol Vis Sci. 2005;46(2):641-646.
58. Lyda W, Eriksen N, Krishna N. Studies of Bruch’s membrane; flow and permeability stud-ies in a Bruch’s membrane-choroid preparation. Am J Ophthalmol. 1957;44(5, Part 2): 362-369; discussion 369-370.
59. Hillenkamp J, Hussain AA, Jackson TL, Constable PA, Cunningham JR, Marshall J. Compartmental analysis of taurine transport to the outer retina in the bovine eye. Invest Ophthalmol Vis Sci. 2004;45(11):4099-4105.
60. Hillenkamp J, Hussain AA, Jackson TL, Cunningham JR, Marshall J. Taurine uptake by human retinal pigment epithelium: Implications for the transport of small solutes between the choroid and the outer retina. Invest Ophthalmol Vis Sci. 2004;45(12): 4529-4534.
61. Kimura M, Araie M, Koyano S. Movement of carboxyfluorescein across retinal pigment epithelium-choroid. Exp Eye Res. 1996;63(1):51-56.
62. Hussain AA, Rowe L, Marshall J. Age-related alterations in the diffusional transport of amino acids across the human Bruch’s-choroid complex. J Opt Soc Am A Opt Image Sci Vis. 2002;19(1):166-172.
63. Ramrattan RS, van der Schaft TL, Mooy CM, de Bruijn WC, Mulder PG, de Jong PT. Morphometric analysis of Bruch’s membrane, the choriocapillaris, and the choroid in aging. Invest Ophthalmol Vis Sci. 1994;35(6):2857-2864.
64. Bird AC, Marshall J. Retinal pigment epithelial detachments in the elderly. Trans Ophthalmol Soc UK. 1986;105(Pt 6):674-682.
65. Hillenkamp J, Hussain AA, Jackson TL, Cunningham JR, Marshall J. The influence of path length and matrix components on ageing characteristics of transport between the choroid and the outer retina. Invest Ophthalmol Vis Sci. 2004;45(5):1493-1498.
66. Moore DJ, Clover GM. The effect of age on the macromolecular permeability of human Bruch’s membrane. Invest Ophthalmol Vis Sci. 2001;42(12):2970-2975.
67. Prince JH, Diesem CD, Eglitis I, Ruskell GL. The Rabbit. In Prince JH, ed. Anatomy and Histology of the Eye and Orbit in Domestic Animals. Springfield, IL: Charles C Thomas; 1960:268.
68. Prince JH, Diesem CD, Eglitis I, Ruskell GL. The Dog. In Prince JH, ed. Anatomy and Histology of the Eye and Orbit in Domestic Animals. Springfield, IL: Charles C Thomas; 1960:73.
69. Prince JH, Diesem CD, Eglitis I, Ruskell GL. The Eyelids. In Prince JH, ed. Anatomy and Histology of the Eye and Orbit in Domestic Animals. Springfield, IL: Charles C Thomas; 1960:46-47.
70. Sugar HS, Riazi A, Schaffner R. The bulbar conjunctival lymphatics and their clinical significance. Trans Am Acad Ophthalmol Otolaryngol. 1957;61(2):212-223.
71. Gausas RE, Gonnering RS, Lemke BN, Dortzbach RK, Sherman DD. Identification of human orbital lymphatics. Ophthal Plast Reconstr Surg. 1999;15(4):252-259.
72. Singh D. Conjunctival lymphatic system. J Cataract Refract Surg. 2003;29(4):632-633.
73. Collin HB. The ultrastructure of conjunctival lymphatic anchoring filaments. Exp Eye Res. 1969;8(2):102-105.
74. Gruntzig J, Schicha H, Kiem J, Becker V, Feinendegen LE. Studies on the lymph drain-age of the eye 5. Quantitative registration of the lymph drainage from the subcon-junctival space with a radioactive tracer (author’s transl). Klin Monatsbl Augenheilkd. 1978;172(6):872-876.
75. Collin HB. Lymphatic drainage of 131-I-albumin from the vascularized cornea. Invest Ophthalmol. 1970;9(2):146-155.
76. Amrite AC, Kompella UB. Size-dependent disposition of nanoparticles and micropar-ticles following subconjunctival administration. J Pharm Pharmacol. 2005;57(12): 1555-1563.
77. Maurice DM, Ota Y. The kinetics of subconjunctival injections. Jpn. J. Ophthalmol. 1978;22:95-100.
78. Robinson MR, Lee SS, Kim H et al. A rabbit model for assessing the ocular barriers to the transscleral delivery of triamcinolone acetonide. Exp Eye Res. 2005;82(3): 479-487.
79. Lee SJ, He W, Robinson SB, Robinson MR, Csaky KG, Kim H. Evaluation of clearance mechanisms with transscleral drug delivery. Invest Ophthalmol Vis Sci. 2010;51(10):5205-5212.
80. Chan JE, Pridgen TA, Csaky KG. Episcleral clearance of sodium fluorescein from a bioerodible sub-tenon’s implant in the rat. Exp Eye Res. 2010;90(4):501-506.
81. Park J, Bungay PM, Lutz RJ et al. Evaluation of coupled convective-diffusive transport of drugs administered by intravitreal injection and controlled release implant. J Control Release. 2005;105(3):279-295.
82. Kim H, Lizak MJ, Tansey G et al. Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging. Ann Biomed Eng. 2005;33(2): 150-164.
83. Sasaki H, Kashiwagi S, Mukai T et al. Drug absorption behavior after periocular injec-tions. Biol Pharm Bull. 1999;22(9):956-960.
84. Bill A. The aqueous humor drainage mechanism in the cynomolgus monkey (Macaca irus) with evidence for unconventional routes. Invest Ophthalmol. 1965;4(5):911-919.
85. Inomata H, Bill A. Exit sites of uveoscleral flow of aqueous humor in cynomolgus mon-key eyes. Exp Eye Res. 1977;25(2):113-118.
86. Krohn J, Bertelsen T. Light microscopy of uveoscleral drainage routes after gelatine injections into the suprachoroidal space. Acta Ophthalmol Scand. 1998;76(5):521-527.
87. Krohn J, Bertelsen T. Corrosion casts of the suprachoroidal space and uveoscleral drain-age routes in the human eye. Acta Ophthalmol Scand. 1997;75(1):32-35.
88. Bill A. The drainage of albumin from the uvea. Exp Eye Res. 1964;75:179-187.
89. Bill A. Movement of albumin and dextran through the sclera. Arch Ophthalmol. 1965;74:248-252.
90. Fautsch MP, Johnson DH. Aqueous humor outflow: What do we know? Where will it lead us? Invest Ophthalmol Vis Sci. 2006;47(10):4181-4187.
91. Bill A. Uveoscleral drainage of aqueous humor: Physiology and pharmacology. Prog Clin Biol Res. 1989;312:417-427.
92. Aihara M, Lindsey JD, Weinreb RN. Aqueous humor dynamics in mice. Invest Ophthalmol Vis Sci. 2003;44(12):5168-5173.
93. Toris CB, Yablonski ME, Wang YL, Camras CB. Aqueous humor dynamics in the aging human eye. Am J Ophthalmol. 1999;127(4):407-412.
94. Inomata H, Bill A, Smelser GK. Unconventional routes of aqueous humor outflow in Cynomolgus monkey (Macaca irus). Am J Ophthalmol. 1972;73(6):893-907.
95. Machemer R. The importance of fluid absorption, traction, intraocular currents, and chorioretinal scars in the therapy of rhegmatogenous retinal detachments. XLI Edward Jackson memorial lecture. Am J Ophthalmol. 1984;98(6):681-693.
96. Marmor MF. Mechanisms of retinal adhesion. Prog Retin Res. 1993;12:179-204.
97. Bill A. A method to determine osmotically effective albumin and gammaglobulin con-centrations in tissue fluids, its application to uvea and a note on effects of capillary “leaks” on tissue fluid dynamics. Acta Physiol Scand. 1968;73(4):511-522.
98. Bill A. Blood circulation and fluid dynamics in the eye. Physiol Rev. 1975;55(3):383-417.
99. Emi K, Pederson JE, Toris CB. Hydrostatic pressure of the suprachoroidal space. Invest Ophthalmol Vis Sci. 1989;30(2):233-238.
100. Mannermaa E, Vellonen KS, Urtti A. Drug transport in corneal epithelium and blood-retina barrier: Emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev. 2006;58(11):1136-1163.
101. Dey S, Mitra AK. Transporters and receptors in ocular drug delivery: Opportunities and challenges. Expert Opin Drug Deliv. 2005;2(2):201-204.
102. Attar M, Shen J, Ling KH, Tang-Liu D. Ophthalmic drug delivery considerations at the cellular level: Drug-metabolising enzymes and transporters. Expert Opin Drug Deliv. 2005;2(5):891-908.
103. Kennedy BG, Mangini NJ. P-glycoprotein expression in human retinal pigment epithe-lium. Mol Vis. 2002;8:422-430.
104. Steuer H, Jaworski A, Elger B et al. Functional characterization and comparison of the outer blood-retina barrier and the blood-brain barrier. Invest Ophthalmol Vis Sci. 2005;46(3):1047-1053.
105. Aukunuru JV, Sunkara G, Bandi N, Thoreson WB, Kompella UB. Expression of multidrug resistance-associated protein (MRP) in human retinal pigment epithelial cells and its interaction with BAPSG, a novel aldose reductase inhibitor. Pharm Res. 2001;18(5):565-572.
106. Cunha-Vaz JG, Maurice DM. The active transport of fluorescein by the retinal vessels and the retina. J Physiol. 1967;191(3):467-486.
107. Maenpaa H, Gegelashvili G, Tahti H. Expression of glutamate transporter sub-types in cultured retinal pigment epithelial and retinoblastoma cells. Curr Eye Res. 2004;28(3):159-165.
108. Miyamoto Y, Del Monte MA. Na(+)-dependent glutamate transporter in human retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 1994;35(10):3589-3598.
109. Sellner PA. The blood-retinal barrier: Leucine transport by the retinal pigment epithe-lium. J Neurosci. 1986;6(10):2823-2828.
110. Sellner PA. The movement of organic solutes between the retina and pigment epithe-lium. Exp Eye Res. 1986;43(4):631-639.
111. Kundaiker S, Hussain AA, Marshall J. Component characteristics of the vectorial transport system for taurine in isolated bovine retinal pigment epithelium. J Physiol. 1996;492 (Pt 2):505-516.
112. Zhang N, Kannan R, Okamoto CT, Ryan SJ, Lee VH, Hinton DR. Characterization of brimonidine transport in retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2006;47(1):287-294.
113. Ito A, Yamaguchi K, Tomita H et al. Distribution of rat organic anion transporting poly-peptide-E (oatp-E) in the rat eye. Invest Ophthalmol Vis Sci. 2003;44(11):4877-4884.
114. Kumar G. Drug metabolizing enzyme systems in the eye. In Reddy I, ed. Ocular Therapeutics and Drug Delivery: A Multi-Disciplinary Approach. Lancaster, PA: Technomic Publishing Company, Inc.; 1996:149-167.
115. Schwartzman ML, Masferrer J, Dunn MW, McGiff JC, Abraham NG. Cytochrome P450, drug metabolizing enzymes and arachidonic acid metabolism in bovine ocular tissues. Curr Eye Res. 1987;6(4):623-630.
116. Shichi H, Nebert DW. Drug metabolism in ocular tissues. In Gram TE, ed. Extrahepatic Metabolism of Drugs and Other Foreign Compounds. Lancaster, UK: MTP Press Limited; 1980:333-363.
117. Duvvuri S, Majumdar S, Mitra AK. Role of metabolism in ocular drug delivery. Curr Drug Metab. 2004;5(6):507-515.
118. Shichi H, Atlas SA, Nebert DW. Genetically regulated aryl hydrocarbon hydroxylase induction in the eye: Possible significance of the drug-metabolizing enzyme system for the retinal pigmented epithelium-choroid. Exp Eye Res. 1975;21(6):557-567.
119. Shichi H. Microsomal electron transfer system of bovine retinal pigment epithelium. Exp Eye Res. 1969;8(1):60-68.
120. Wrighton SA, Thummel KE. CYP3A. In Levy RH, Thummel KE, Trager WF, Hansten PD, Eichelbaum M, eds. Metabolic Drug Interactions. Philadelphia, PA: Lippincott Williams & Wilkins; 2000:115-133.
121. Marshall J. The ageing retina: Physiology or pathology. Eye. 1987;1(Pt 2):282-295.
122. Diment S, Eidelman M, Rodriguez GM, Orlow SJ. Lysosomal hydrolases are pres-ent in melanosomes and are elevated in melanizing cells. J Biol Chem. 1995;270(9): 4213-4215.
123. Hayasaka S. Lysosomal enzymes in ocular tissues and diseases. Surv Ophthalmol. 1983;27(4):245-258.
124. Hayasaka S, Shiono T. alpha-Fucosidase, alpha-mannosidase and beta-N-acetylglucos-aminidase of the bovine retinal pigment epithelium. Exp Eye Res. 1982;34(4):565-569.
125. Lloyd JB. Lysosome membrane permeability: Implications for drug delivery. Adv Drug Deliv Rev. 2000;41(2):189-200.
126. Lloyd JB. Studies on the permeability of rat liver lysosomes to carbohydrates. Biochem J. 1969;115(4):703-707.
127. Lee SS, Hughes P, Ross AD, Robinson MR. Biodegradable implants for sustained drug release in the eye. Pharm Res. 2010;27(10):2043-2053.
128. Lee SS, Hughes P, Ross AD, Robinson MR. Advances in biodegradable ocular drug delivery systems. In Kompella U, Edelhauser H, eds. Drug Product Development for the Back of the Eye. New York, NY: Springer/American Association of Pharmaceutical Scientists; 2011:185-230.
129. Robinson MR, Lee SS, Kim H et al. A rabbit model for assessing the ocular barriers to the transscleral delivery of triamcinolone acetonide. Exp Eye Res. 2006;82(3):479-487.
130. Jermak CM, Dellacroce JT, Heffez J, Peyman GA. Triamcinolone acetonide in ocular therapeutics. Surv Ophthalmol. 2007;52:503-522.
131. Gasiorowski JZ, Russell P. Biological properties of trabecular meshwork cells. Exp Eye Res. 2009;88:671-675.
132. Pontes de Carvalho RA, Krausse ML, Murphree AL, Schmitt EE, Campochiaro PA, Maumenee IH. Delivery from episcleral exoplants. Invest Ophthalmol Vis Sci. 2006;47(10):4532-4539.
133. Kato A, Kimura H, Okabe K, Okabe J, Kunou N, Ogura Y. Feasibility of drug delivery to the posterior pole of the rabbit eye with an episcleral implant. Invest Ophthalmol Vis Sci. 2004;45:238-244.
134. Alvarez-Figueroa MJ, Blanco-Mendez J. Transdermal delivery of methotrexate: Iontophoretic delivery from hydrogels and passive delivery from microemulsions. Int J Pharm. 2001;215:57-65.
135. Eljarrat-Binstock E, Orucov F, Aldouby Y, Frucht-Pery J, Domb AJ. Charged nanoparticles delivery to the eye using hydrogel iontophoresis. J Control Release. 2008;126:156-161.
136. Behar-Cohen FF, Parel JM, Pouliquen Y et al. Iontophoresis of dexamethasone in the treatment of endotoxin-induced-uveitis in rats. Exp Eye Res. 1997;65:533-545.
137. Lam TT, Edward DP, Zhu XA, Tso M.O. Transscleral iontophoresis of dexamethasone. Arch Ophthalmol. 1989;107:1368-1371.
138. Eljarrat-Binstock E, Raiskup F, Frucht-Pery J, Domb AJ. Transcorneal and transscleral iontophoresis of dexamethasone phosphate using drug loaded hydrogel. J Control Release. 2005;106:386-390.
139. Hastings MS, Li SK, Miller DJ, Bernstein PS, Mufson D. Visulex: Advancing ionto-phoresis for effective noninvasive backto-the-eye therapeutics. Drug Delivery Tech. 2004;4:53-57.
140. Behar-Cohen FF, Halhal M, Benezra D, Chauvaud D, Renard G. Reversal of corneal graft rejection by iontophoresis of methylprednisolone. Invest Ophthalmol Vis Sci. 2002;43:U504
141. Chauvaud D, Behar-Cohen FF, Parel JM, Renard G. Transscleral iontophoresis of cort-coosteroids: Phase II clinical trial. Invest Ophthalmol Vis Sci. 2000;41:S79
142. Halhal M, Renard G, Bejjani RA, Behar-Cohen F. Corneal graft rejection and corticoid iontophoresis: Three case reports. J Fr Ophtalmol. 2003;26:391-395.
143. Halhal M, Renard G, Courtois Y, Benezra D, Behar-Cohen F. Iontophoresis: From the lab to the bed side. Exp Eye Res. 2004;78:751-757.
144. Pescina S, Ferrari G, Govoni P et al. In-vitro permeation of bevacizumab through human sclera: Effect of iontophoresis application. J Pharm Pharmacol. 2010;62(9):1189-1194.
145. Kim H, Robinson MR, Lizak MJ et al. Controlled drug release from an ocular implant: An evaluation using dynamic three-dimensional magnetic resonance imaging. Invest Ophthalmol Vis Sci. 2004;45(8):2722-2731.
146. Li SK, Molokhia SA, Jeong EK. Assessment of subconjunctival delivery with model ionic permeants and magnetic resonance imaging. Pharm Res. 2004;21(12):2175-2184.
147. Olsen TW, Feng X, Wabner K et al. Cannulation of the suprachoroidal space: A novel drug delivery methodology to the posterior segment. Am J Ophthalmol. 2006;142(5):777-787.