Abstract
The physiological characteristics make effective drug delivery very challenging. Various structures such as the cornea, conjunctival epithelium, blood-retinal barrier (BRB), and the retinal epithelium block or severely reduce the concentration of drugs that can reach particular locations in the eye. Because of this, in vitro models that can effectively model each of these barriers are highly desirable. Such in vitro modeling allows researchers to minimize the use of animal studies, as drug delivery experiments require frequent euthanization. As a substitute for animal experiments, various types of in vitro models have been developed that are made up of primary cell cultures or immortalized cell lines. These cell lines allow for the detailed study of the individual processes that determine the ability of drugs and drug delivery systems to reach their desired locations in therapeutic concentrations. This chapter discusses various examples of such cell lines and their applicability in various drug delivery studies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hornof M, Toropainen E, Urtti A (2005) Cell culture models of the ocular barriers. Eur J Pharm Biopharm 60(2):207–225
Offord EA et al (1999) Immortalized human corneal epithelial cells for ocular toxicity and inflammation studies. Invest Ophthalmol Vis Sci 40(6):1091–1101
Urtti A, Salminen L (1993) Minimizing systemic absorption of topically administered ophthalmic drugs. Surv Ophthalmol 37(6):435–456
Gardner TW et al (1999) The molecular structure and function of the inner blood-retinal barrier. Doc Ophthalmol 97(3):229–237
Kahn C et al (1993) Human corneal epithelial primary cultures and cell lines with extended life span: in vitro model for ocular studies. Invest Ophthalmol Vis Sci 34(12):3429–3441
Grolik M et al (2011) Regeneration of corneal epithelium using keratin modified chitosan membranes. Przegl Lek 69(10):992–997
Huang A, Tseng S, Kenyon K (1989) Paracellular permeability of corneal and conjunctival epithelia. Invest Ophthalmol Vis Sci 30(4):684–689
Hämäläinen K et al (1997) Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci 38(3):627–634
Kruszewski F, Walker T, DiPasquale L (1997) Evaluation of a human corneal epithelial cell line as an in vitro model for assessing ocular irritation. Toxicol Sci 36(2):130–140
Araki-Sasaki K et al (1995) An SV40-immortalized human corneal epithelial cell line and its characterization. Invest Ophthalmol Vis Sci 36(3):614–621
Huhtala A et al (2002) Comparison of an immortalized human corneal epithelial cell line and rabbit corneal epithelial cell culture in cytotoxicity testing. J Ocul Pharmacol Ther 18(2):163–175
Toropainen E et al (2003) Paracellular and passive transcellular permeability in immortalized human corneal epithelial cell culture model. Eur J Pharm Sci 20(1):99–106
Kitazawa K et al (2013) Establishment of a human corneal epithelial cell line lacking the functional TACSTD2 gene as an in vitro model for gelatinous drop-like dystrophy. Invest Ophthalmol Vis Sci 54(8):5701–5711
Kinoshita S et al (2012) Establishment of a human conjunctival epithelial cell line lacking the functional Tacstd2 gene (an American ophthalmological society thesis). Trans Am Ophthalmol Soc 110:166
Movahedan H, Anvari-Ardekani HR, Nowroozzadeh MH (2013) Limbal stem cell transplantation for gelatinous drop-like corneal dystrophy. J Ophthalmic Vis Res 8(2):107
Alekseev O et al (2014) Nonthermal dielectric barrier discharge (DBD) plasma suppresses herpes simplex virus type 1 (HSV-1) replication in corneal epithelium. Translat Vis Sci Technol 3(2)
Zhu X et al (2012) Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery. Mol Vis 18:1973
Yang J et al (2014) Dithiol-PEG-PDLLA micelles: preparation and evaluation as potential topical ocular delivery vehicle. Biomacromolecules 15(4):1346–1354
Griffith M et al (1999) Functional human corneal equivalents constructed from cell lines. Science 286(5447):2169–2172
Engelke M et al (2013) A human hemi-cornea model for eye irritation testing: quality control of production, reliability and predictive capacity. Toxicol In Vitro 27(1):458–468
Tegtmeyer S, Papantoniou I, Müller-Goymann CC (2001) Reconstruction of an in vitro cornea and its use for drug permeation studies from different formulations containing pilocarpine hydrochloride. Eur J Pharm Biopharm 51(2):119–125
Diebold Y et al (2003) Characterization of a spontaneously immortalized cell line (IOBA-NHC) from normal human conjunctiva. Invest Ophthalmol Vis Sci 44(10):4263–4274
Gao J et al (2013) Mitochondrial permeability transition pore in inflammatory apoptosis of human conjunctival epithelial cells and T cells: effect of cyclosporin a. Invest Ophthalmol Vis Sci 54(7):4717–4733
Brasnu E et al (2008) Comparative study on the cytotoxic effects of benzalkonium chloride on the Wong-Kilbourne derivative of Chang conjunctival and IOBA-NHC cell lines. Mol Vis 14:394–402
Cunha-Vaz JG (1997) The blood-ocular barriers: past, present, and future. Doc Ophthalmol 93(1–2):149–157
Bochot A, Couvreur P, Fattal E (2000) Intravitreal administration of antisense oligonucleotides: potential of liposomal delivery. Prog Retin Eye Res 19(2):131–147
Jumbe NL, Miller MH (2003) Ocular drug transfer following systemic drug administration. Drugs Pharm Sci 130:109–134
Maurice D, Mishima S (1984) Ocular pharmacokinetics. In: Pharmacology of the eye. Springer, New York, pp 19–116
Mitra AK (2003) Ophthalmic drug delivery systems. Marcel Dekker, New York
Marmor M (1998) Structure, function, and disease of the retinal pigment epithelium. In Marmor MF, Wolfensberger TJ (eds) The retinal pigment epithelium, vol 3. Oxford University Press, New York, p 12
Duvvuri S, Majumdar S, Mitra AK (2003) Drug delivery to the retina: challenges and opportunities. Expert Opin Biol Ther 3(1):45–56
Sunkara G, Kompella UB (2003) Membrane transport processes in the eye. Drugs Pharm Sci 130:13–58
Eldem T et al (2002) Cell cultures of the retinal pigment epithelium to model the blood–retinal barrier for retinal drug and gene delivery. Cell culture models of biological barriers: in vitro test systems for drug absorption and delivery, 2002, p 271
Davis AA et al (1995) A human retinal pigment epithelial cell line that retains epithelial characteristics after prolonged culture. Invest Ophthalmol Vis Sci 36(5):955–964
Mannerström M et al (2001) The phagocytosis of rod outer segments is inhibited by selected drugs in retinal pigment epithelial cell cultures. Pharmacol Toxicol 88(1):27–33
Hyvönen Z et al (2000) Novel cationic amphiphilic 1, 4-dihydropyridine derivatives for DNA delivery. Biochim Biophys Acta 1509(1):451–466
Dunn KC et al (1998) Use of the ARPE-19 cell line as a model of RPE polarity: basolateral secretion of FGF5. Invest Ophthalmol Vis Sci 39(13):2744–2749
Bodnar AG et al (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279(5349):349–352
Jiang X-R et al (1999) Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype. Nat Genet 21(1):111–114
Rambhatla L et al (2002) In vitro differentiation capacity of telomerase immortalized human RPE cells. Invest Ophthalmol Vis Sci 43(5):1622–1630
Rossem V, Vos D (1998) Polarized secretion of IL‐6 and IL‐8 by human retinal pigment epithelial cells. Clin Exp Immunol 112(1):34–43
Gillies MC, Su T (1995) Interferon-α 2b enhances barrier function of bovine retinal microvascular endothelium in vitro. Microvasc Res 49(3):277–288
Gillies MC et al (1997) Effect of high glucose on permeability of retinal capillary endothelium in vitro. Invest Ophthalmol Vis Sci 38(3):635–642
Gardner TW (1995) Histamine, ZO-1 and increased blood-retinal barrier permeability in diabetic retinopathy. Trans Am Ophthalmol Soc 93:583
Gardner T et al (1996) Histamine reduces ZO-1 tight-junction protein expression in cultured retinal microvascular endothelial cells. Biochem J 320:717–721
Yaccino JAM et al (1997) Physiological transport properties of cultured retinal microvascular endothelial cell monolayers. Curr Eye Res 16(8):761–768
Chang YS et al (2000) Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties. Microvasc Res 59(2):265–277
Lakshminarayanan S et al (2000) Effect of VEGF on retinal microvascular endothelial hydraulic conductivity: the role of NO. Invest Ophthalmol Vis Sci 41(13):4256–4261
Antonetti DA et al (2002) Hydrocortisone decreases retinal endothelial cell water and solute flux coincident with increased content and decreased phosphorylation of occludin. J Neurochem 80(4):667–677
Hosoya K-I et al (2001) Conditionally immortalized retinal capillary endothelial cell lines (TR-iBRB) expressing differentiated endothelial cell functions derived from a transgenic rat. Exp Eye Res 72(2):163–172
Shen J et al (2003) Evaluation of an immortalized retinal endothelial cell line as an in vitro model for drug transport studies across the blood-retinal barrier. Pharm Res 20(9):1357–1363
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Solanki, A., Desai, S., Grover, A., Hirani, A., Pathak, Y., Sutariya, V. (2016). Ocular Drug Delivery: Impact of In Vitro Cell Culture Models. In: Pathak, Y., Sutariya, V., Hirani, A. (eds) Nano-Biomaterials For Ophthalmic Drug Delivery. Springer, Cham. https://doi.org/10.1007/978-3-319-29346-2_21
Download citation
DOI: https://doi.org/10.1007/978-3-319-29346-2_21
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-29344-8
Online ISBN: 978-3-319-29346-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)