Ophthalmic drug delivery considerations at the cellular level: drug-metabolising enzymes and transporters

Bibliography

• the US: prevalence of adult vision impairment and age-related eye disease in America. Prevent Blindness America (2002).
   Google Scholar
• ZIMMERMAN TJ, LEADER B, KAUFMAN HE: Advances in ocular pharmacology. Ann. Rev Pharmacol Toxicol (1980) 20:415–428.
   Google Scholar
• LEE VH: Precorneal, corneal and postcorneal factors. In: Ophthalmic Drug Delivery Systems. AK Mitra (Ed.), Marcel Dekker, Inc., New York, NY, USA (1993):59–81.
   Google Scholar
• DUVVURI S, MAJUMDAR S, MITRA AK: Role of metabolism in ocular drug delivery. Curr. Drug Metab. (2004) 5:507–515.
   Google Scholar
• PARKINSON A: An overview of current cytochrome P450 technology for assessing the safety and efficacy of new materials. Toxicol. Pathol. (1996) 24:48–57.
   Google Scholar
• PARKINSON A: Biotransformation of xenobiotics. In: Casarett & Doulic Toxicology: the basic science of poisons. CD Klaassen (Ed.), McGraw-Hill, New York, NY, USA (1996):113–186.
   Google Scholar
• WILKINSON GR: Pharmacokinetics. In: Goodman and Gilman's: the pharmacological basis of therapeutics. AJ H LE L A Goodman Gilman (Eds), McGraw-Hill, New York, NY, USA (2001)3–30.
   Google Scholar
• SHICHI H: Microsomal electron transfer system of bovine retinal pigment epithelium. Exp. Eye Res. (1969) 8:60–68.
   Google Scholar
• •The first published report of a microsomal electron transfer system in any ocular tissue.
   Google Scholar
• MCAVOY M, SINGH AK, SHICHI H:hi situ hybridization of Cyplal, Cypla2 and Ah receptor mRNAs expressed in murine ocular tissues. Exp. Eye Res. (1996) 62:449–452.
   Google Scholar
• ZHAO C, SHICHI H: Immunocytochemical study of cytochrome P450 (1A1/1A2) induction in murine ocular tissues. Exp. Eye Res. (1995) 60:143–152.
   Google Scholar
• XIE Q, ZHANG QY, ZHANG Y et al: Induction of mouse CYP2J by pyrazole in the eye, kidney, liver, lung, olfactory mucosa, and small intestine but not in the heart. Drug Metab. Dispas. (2000) 28:1311–1316.
   Google Scholar
• TSAO CC, COULTER SJ, CHIEN A et al.: Identification and localization of five CYP2Cs in murine extrahepatic tissues and their metabolism of arachidonic acid to regio- and stereoselective products. Pharmacol Exp. Ther. (2001) 299:39–47.
   Google Scholar
• ATTAR M, LING KH, TAN G-LIUDD et al: Cytochrome P450 3A expression and activity in the rabbit lacrimal gland: glucocorticoid modulation and the impact on androgen metabolism. Invest. Ophthalmol. Vis. Sci. (2005) (In press).
   Google Scholar
• •The first published report of CYP3A expression and activity, an enzyme responsible for steroid deactivation, in the lacrimal gland, a steroid sensitive tissue.
   Google Scholar
• ATTAR M, LEE, TAN G-LIUDS et al.: Characterization of cytochrome P450 1A, 2D and 3A in the rabbit eye. Presented at the sixth annual meeting of the Association of Ophthalmolgy and Pharmacology Therapeutics, Kaui, HI, USA (2003).
   Google Scholar
• MASTYUGIN V, AVERSA E, BONAZZI A et al: Hypoxia-induced production of 12-hydroxyeicosanoids in the corneal epithelium: involvement of a cytochrome P4504B1 isoform. Pharmacol. Exp. Ther. (1999) 289:1611–1619.
   Google Scholar
• STOILOV I, AKARSU AN, SARFARAZI M: Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum. Mol. Genet. (1997) 6:641–647.
   Google Scholar
• STOILOV I, AKARSU AN, ALOZIE I et al.: Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1. Am. J. Hum. Genet. (1998) 62:573–584.
   Google Scholar
• WAXMAN DJ, ATTISANO C, GUENGERICH FP et al.: Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6 beta-hydroxylase cytochrome P450 enzyme. Arch. Biochem. Biophys. (1988) 263:424–436.
   Google Scholar
• MADHU C, DINH V, BABUSIS D et al: Tissue specific distribution of cytochrome P450 isozymes in the monkey eye. Annual meeting of the Association for Research in Vision and Ophthalmology Proceedings, Fort Lauderdale, Florida, USA (1999).
   Google Scholar
• MADHU C, DINH V, BABUSIS D et al: Expression of cytochrome P450 isoenzymes in dog and human eye. Fourteenth annual meeting of the International Socie0, for the Study of Xenobiotics Proceedings (1999).
   Google Scholar
• LEE VH, CHIEN DS, SASAKI H: Ocularketone reductase distribution and its role in the metabolism of ocularly applied levobunolol in the pigmented rabbit. Pharmacol Exp. Ther. (1988) 246:871–878.
   Google Scholar
• BERKMAN CE, PARK SB, WRIGHTON SA et al.: LI vitro-in vivo correlations of human (S)-nicotine metabolism. Biochem. Pharmacol (1995) 50:565–570.
   Google Scholar
• HUANG DY, FURUKAWA A, ICHIKAWA Y: Molecular cloning of retinal oxidase/aldehyde oxidase cDNAs from rabbit and mouse livers and functional expression of recombinant mouse retinal oxidase cDNA in Escherichia coli. Arch. Biochem. Biophys. (1999) 364:264–272.
   Google Scholar
• SHIMADA S, MISHIMA H, KITAMURA S et al.: Nicotinamide Noxide reductase activity in bovine and rabbit eyes. Invest. Ophthalmol. 1/is. Li. (1987) 28:1204–1206.
   Google Scholar
• ACHEAMPONG AA, CHIEN DS, LAM S et al.: Characterization of brimonidine metabolism with rat, rabbit, dog, monkey and human liver fractions and rabbit liver aldehyde oxidase. Xenobiotica (1996) 26:1035–1055.
   Google Scholar
• ACHEAMPONG AA, SHACKLETON M, TANG-LIU DD: Comparative ocular pharmacokinetics of brimonidine after a single dose application to the eyes of albino and pigmented rabbits. Drug Metab. Dispos. (1995) 23:708–712.
   Google Scholar
• TANG-LIU DD, LIU S, NEFF J et al: Disposition of levobunolol after an ophthalmic dose to rabbits. J. Pharm. Sci. (1987) 76:780–783.
   Google Scholar
• SCHOENWALD RD, ZHU J: The ocular pharmacokinetics of ketanserin and its metabolite, ketanserinol, in albino rabbits. J. Ocul. Pharmacol Ther. (2000) 16:481–495.
   Google Scholar
• TANG-LIU DD, SHACKLETON M, RICHMAN JB: Ocular metabolism of levobunolol. Or& Pharmacol (1988) 4:269–278.
   Google Scholar
• TANG-LIU DD, RICHMAN JB: The effect of pilocarpine on ocular levobunolol absorption from ophthalmic solutions. J. Ocul. Pharmacol (1994) 10:605–615.
   Google Scholar
• ESSNER E, GORRIN GM, GRIEWSKI RA: Localization of lysosomal enzymes in retinal pigment epithelium of rats with inherited retinal dystrophy. Invest. Ophthalmol 1/is. Sci. (1978) 17:278–288.
   Google Scholar
• LEE VH, CHANG SC, OSHIRO CM et al.: Ocular esterase composition in albino and pigmented rabbits: possible implications in ocular prodrug design and evaluation. Curr. Eye Res. (1985) 4:1117–1125.
   Google Scholar
• STAMPFLI HF, QUON CY: Polymorphic metabolism of flestolol and other ester containing compounds by a carboxylesterase in New Zealand white rabbit blood and cornea. Res. Commun. Mol. Pathol Pharmacol (1995) 88:87–97.
   Google Scholar
• LEE VH, IIMOTO DS, TAKEMOTO KA: Subcellular distribution of esterases in the bovine eye. Curr. Eye Res. (1982) 2:869–876.
   Google Scholar
• LEE VH, MORIMOTO KW, STRATFORD RE Jr: Esterase distribution in the rabbit cornea and its implications in ocular drug bioavailability. Biopharm. Drug Dispos. (1982) 3:291–300.
   Google Scholar
• ANDERSON JA, DAVIS WL, WET CP: Site of ocular hydrolysis of a prodrug, dipivefrin, and a comparison of its ocular metabolism with that of the parent compound, adrenaline. Invest. Ophthalmol 1/is. Sci. (1980) 19:817–823.
   Google Scholar
• MINDEL JS, YABLONSKI ME, TAVITIAN HO et al: Dipivefrin and echothiophate. Efficacy of combined use in human beings. Arch. Ophthalmol. (1981) 99:1583–1586.
   Google Scholar
• PUTNAM ML, SCHOENWALD RD, DUFFEL MW et al: Ocular disposition of aminozolamide in the rabbit eye. Invest. Ophthalmol 1/is. Sci. (1987) 28:1373–1382.
   Google Scholar
• CAMPBELL DA, SCHOENWALD RD, DUFFEL MW et al: Characterization of arylamine acetyltransferase in the rabbit eye. Invest. Ophthalmol 1/is. Li. (1991) 32:2190–2200.
   Google Scholar
• SRIVASTAVA SK, SINGHAL SS, BAJPAI KK et al.: A group of novel glutathione ..Ctransferase isozymes showing high activity towards 4-hydroxy-2-nonenal are present in bovine ocular tissues. Exp. Eye Res. (1994) 59:151–159.
   Google Scholar
• SINGHAL SS, GODLEY BE, CHANDRA A et al: Induction of glutathione ..Ctransferase hGST 5.8 is an early response to oxidative stress in RPE cells. Invest. Ophthalmol 1/is. Sci. (1999) 40: 2652–2659.
   Google Scholar
• DEY S, ANAND BS, PATEL J et al.: Transporters/receptors in the anterior chamber: pathways to explore ocular drug delivery strategies. Expert Opin. Biol. Ther. (2003) 3:23–44.
   Google Scholar
• ITO A, YAMAGUCHI K, TOMITA H et al: Distribution of rat organic anion transporting polypeptide-E (oatp-E) in the rat eye. Invest. Ophthalmol 1/is. Sci. (2003) 44:4877–4884.
   Google Scholar
• UEDA H, HORIBE Y, KIM KJ et al: Functional characterization of organic cation drug transport in the pigmented rabbit conjunctiva. Invest. Ophthalmol 1/is. Sci. (2000) 41:870–876.
   Google Scholar
• MAJUMDAR S, TIRUCHERAI GS, PAL D et al.: Functional differences in nucleoside and nucleobase transporters expressed on the rabbit corneal epithelial cell line (SIRC) and isolated rabbit cornea. AAPS PharmSci. (2003) 5:E15.
   Google Scholar
• DUVVURI S, MAJUMDAR S, MITRA AK: Drug delivery to the retina: challenges and opportunities. Expert Opin. Biol. Ther. (2003) 3:45–56.
   Google Scholar
• OCHELTREE SM, KEEP RF, SHEN H et al: Preliminary investigation into the expression of proton-coupled oligopeptide transporters in neural retina and retinal pigment epithelium (RPE): lack of functional activity in RPE plasma membranes. Pharm. Res. (2003) 20:1364–1372.
   Google Scholar
• RAJAN PD, KEKUDA R, CHANCY CD et al: Expression of the extraneuronal monoamine transporter in RPE and neural retina. Curl: Eye Res. (2000) 20:195–204.
   Google Scholar
• MAJUMDAR S, MACHA S, PAL D et al: Mechanism of ganciclovir uptake by rabbit retina and human retinal pigmented epithelium cell line ARPE-19. Curr. Eye Res. (2004) 29:127–136.
   Google Scholar
• DEY S, GUNDA S, MITRA AK: Pharmacokinetics of erythromycin in rabbit corneas after single-dose infusion: role of P-glycoprotein as a barrier to in vivo ocular drug absorption. J. Pharmacol Exp. Ther. (2004) 311:246–255.
   Google Scholar
• DEY S, PATEL J, ANAND BS et al: Molecular evidence and functional expression of P-glycoprotein (MDR1) in human and rabbit cornea and corneal epithelial cell lines. Invest. Ophthalmol 1/is. Sci. (2003) 44:2909–2918.
   Google Scholar
• KAWAZU K, YAMADA K, NAKAMURA M et al.: Characterization of cyclosporin A transport in cultured rabbit corneal epithelial cells: P-glycoprotein transport activity and binding to cyclophilin. Invest. Ophthalmol 1/is. Sci. (1999) 40:1738–1744.
   Google Scholar
• YANG JJ, KIM KJ, LEE VH: Role of P-glycoprotein in restricting propranolol transport in cultured rabbit conjunctival epithelial cell layers. Pharm. Res. (2000) 17:533–538.
   Google Scholar
• SAHA P, YANG JJ, LEE VH: Existence of a P-glycoprotein drug efflux pump in cultured rabbit conjunctival epithelial cells. Invest. Ophthalmol 1/is. Sci. (1998) 39:1221–1226.
   Google Scholar
• •The first published report of P-gp expression and activity in the conjunctival epithelium.
   Google Scholar
• GREENWOOD J: Characterization of a rat retinal endothelial cell culture and the expression of P-glycoprotein in brain and retinal endothelium in vitro. J.Neuroimmunol. (1992) 39:123–132.
   Google Scholar
• KENNEDY BG, MANGINI NJ: P-glycoprotein expression in human retinal pigment epithelium. Mo/ 1/is. (2002) 8:422–430.
   Google Scholar
• AUKUNURU JV, SUNKARA G, BANDI N et al.: Expression of multi-drug resistance-associated protein (MRP) in human retinal pigment epithelial cells and its interaction with BAPSG, a novel aldose reductase inhibitor. Pharm. Res. (2001) 18:565–572.
   Google Scholar
• LIN JH, LU AY: Inhibition and inductionof cytochrome P450 and the clinical implications. Clin. Pharmacokinet. (1998) 35:361–390.
   Google Scholar
• SACHSE C, BROCKMOLLER J, BAUER S et al.: Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am. J. Hum. Genet. (1997) 60:284–295.
   Google Scholar
• PHILLIPS KA, VEENSTRA DL, OREN E et al.: Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA (2001) 286:2270–2279.
   Google Scholar
• LIN JH, LU AY: Role of pharmacokineticsand metabolism in drug discovery and development. Pharmacol Rev. (1997) 49:403–449.
   Google Scholar
• EDEKI TI, HE H, WOOD AJ: Pharmacogenetic explanation for excessive beta-blockade following timolol eye drops. Potential for oral-ophthalmic drug interaction. JAMA (1995) 274:1611–1613.
   Google Scholar
• ISHII Y, NAKAMURA K, TSUTSUMI K et al.: Drug interaction between cimetidine and timolol ophthalmic solution: effect on heart rate and intraocular pressure in healthy Japanese volunteers. J. Clin. Pharmacol. (2000) 40:193–199.
   Google Scholar
• NOVACK GD: Excessive B-blockade withtimolol eye drops. JAMA (1996) 275:985.
   Google Scholar
• PUTTERMAN GJ, DAVIDSON J, ALBERT J: Lack of metabolism of timolol by ocular tissues. J. Or& Pharmacol (1985) 1:287–296.
   Google Scholar
• PAI HV, KOMMADDI RP, CHINTA SJ et al.: A frameshift mutation and alternate splicing in human brain generate a functional form of the pseudogene cytochrome P4502D7 that demethylates codeine to morphine. Biol. Chem. (2004) 279:27383–27389.
   Google Scholar
• SEKINE Y, HOMMURA S, HARADA S: Frequency of glutathione-Stransferase 1 gene deletion and its possible correlation with cataract formation. Exp. Eye Res. (1995) 60:159–163.
   Google Scholar
• JURONEN E, TASA G, VEROMANN S et al.: Polymorphic glutathione ..Ctransferases as genetic risk factors for senile cortical cataract in Estonians. Invest. Ophthalmol 1/is. Sci. (2000) 41:2262–2267.
   Google Scholar
• SCOTT IU, FLYNN HW MILLER Det al: Exogenous endophthalmitis caused by amphotericin B-resistant Paecilomyces lilacinus: treatment options and visual outcomes. Arch. Ophthalmol (2001) 119:916–919.
   Google Scholar
• THOMAS PA: Fungal infections of the cornea. Eye (2003) 17:852–862.
   Google Scholar
• ARTHUR RR, DREW RH, PERFECT JR: Novel modes of antifungal drug administration. Expert Opin. Investig. Drugs (2004) 13:903–932.
   Google Scholar
• TOLER SM: Oxidative stress plays an important role in the pathogenesis of drug-induced retinopathy. Exp. Biol. Med.(Maywood) (2004) 229:607–615.
   Google Scholar
• 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) 21:557–567.
   Google Scholar
• MADHU C, DINH V, BABUSIS D et al:Cytochrome P450 isozyme activities in rabbit ocular tissues. Thirteenth annual meeting of the International Society for the Study of Xenobiotics Proceedings, Cairns, Australia (1998).
   Google Scholar
• MADAN A, GRAHAM RA, CARROLL KM et al.: Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab. Dispos. (2003) 31:421–431.
   Google Scholar
• MATSUMOTO K, KISHIDA K, MANABE R et al.: Induction of cytochrome P450 in the rabbit eye by phenobarbital, as detected immunohistochemically. Curr. Eye Res. (1987) 6:847–854.
   Google Scholar
• TANAKA H, HIRAYAMA I, TAKEHANA M et al.: Cytochrome P450 expression in rat ocular tissues and its induction by phenobarbital. I. Health Li. (2002) 48:346–349.
   Google Scholar
• NELSON KC, ARMSTRONG JS, MORIARTY S et al.: Protection of retinal pigment epithelial cells from oxidative damage by oltipraz, a cancer chemopreventive agent. Invest. Ophthalmol 1/is. Li. (2002) 43:3550–3554.
   Google Scholar
• WEI CP, ANDERSON JA, LEOPOLD I: Ocular absorption and metabolism of topically applied adrenaline and a dipivalyl ester of adrenaline. Invest. Ophthalmol 1/is. Li. (1978) 17:315–321.
   Google Scholar
• SJOQUIST B, STJERNSCHANTZ J: Ocular and systemic pharmacokinetics of latanoprost in humans. Surv. Ophthalmol (2002) 47 (Suppl. 1):56–512.
   Google Scholar
• DRUZGALA P, WU WM, BODOR N: Ocular absorption and distribution of loteprednol etabonate, a soft steroid, in rabbit eyes. Curr. Eye Res. (1991) 10:933–937.
   Google Scholar
• KASS M, CHEETHAM J, DUZMAN E et al.: The ocular hypertensive effect of 0.25% fluorometholone in corticosteroid responders. Am. J. Ophthalmol (1986) 102:159–163.
   Google Scholar
• HAGENBUCH B, MEIER PJ: The superfamily of organic anion transporting polypeptides. Biochim. Biophys. Acta (2003) 1609:1–18.
   Google Scholar
• WOLDEMUSSIE E, RUIZ G, WIJONO M et al.: Neuroprotection of retinal ganglion cells by brimonidine in rats with laser-induced chronic ocular hypertension. Invest. Ophthalmol 1/is. (2001) 42:2849–2855.
   Google Scholar
• YOSHIDA S, HONDA M, YOSHIDA A et al.: Novel mutation in ABCC6 gene in a Japanese pedigree with pseudoxanthoma elasticum and retinitis pigmentosa. Eye (2005) 19:215–217.
   Google Scholar
• RINGPFEIL F, LEBWOHL MG, CHRISTIANO AM et al: Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc. Nati Acad. Sci.USA (2000) 97:6001–6006.
   Google Scholar
• SHICHI H, GAASTERLAND DE, JENSEN NM et al.: Ah locus: genetic differences in susceptibility to cataracts induced by acetaminophen. Science (1978) 200:539–541.
   Google Scholar
• ZHAO C, SHICHI H: Prevention of acetaminophen-induced cataract by a combination of diallyl disulfide and Nacetylcysteine.Pharmacol Ther.(1998) 14:345–355.
   Google Scholar
• AMIN RH, SHICHI H: Cytotoxic metabolite of acetaminophen, Nacetyl-p-benzoquinone imine, produces cataract in DBA2 mice. J. Ocul. Pharmacol Ther. (1999) 15:537–545.
   Google Scholar
• GERSON RJ, MACDONALD JS, ALBERTS AW et al.: On the aetiology of subcapsular lenticular opacities produced in dogs receiving HMG-CoA reductase inhibitors. Exp. Eye Res. (1990) 50:65–78.
   Google Scholar
• RAO PV, ROBISON WG BETTELHEIM F et al: Role of small GTP-binding proteins in lovastatin-induced cataracts. Invest. Ophthalmol. Vis. Sci. (1997) 38:2313–2321.
   Google Scholar
• SMEETH L, HUBBARD R, FLETCHER AE: Cataract and the use of statins: a case-control study. QJM(2003) 96: 337–343.
   Google Scholar
• BOCCUZZI SJ, BOCANEGRA TS, WALKER JF et al.: Long-term safety and efficacy profile of simvastatin. Am. J. Cardiol (1991) 68:1127–1131.
   Google Scholar
• HARRIS ML, BRON AJ, BROWN NA et al.: Absence of effect of simvastatin on the progression of lens opacities in a randomised placebo-controlled study. Oxford Cholesterol Study Group. BE J. Ophthalmol (1995) 79:996–1002.
   Google Scholar
• EINARSON TR, METGE CJ, ISKEDJIAN M et al.: An examination of the effect of cytochrome P450 drug interactions of hydroxymethylglutaryl-coenzyme A reductase inhibitors on healthcare utilization: a Canadian population-based study. Chit Ther. (2002) 24:2126–2136.
   Google Scholar
• PATTON WP, ROUTLEDGE MN, JONES GD et al.: Retinal pigment epithelial cell DNA is damaged by exposure to benzo [alpyrene, a constituent of cigarette smoke. Exp. Eye Res. (2002) 74:513–522.
   Google Scholar
• ZHANG Y, WU X, GUO D et al: Two-step error-prone bypass of the (÷)- and (-)-trans-anti-BPDE-N2-dG adducts by human DNA polymerases eta and kappa. Mutat Res. (2002) 510:23–35.
   Google Scholar
• SARDESAI VM: Molybdenum: an essential trace element. Nutt Clin. Pract. (1993) 8:277–281.
   Google Scholar
• PARINI R, BRISCIOLI V, CARUSO U et al.: Spherophakia associated with molybdenum cofactor deficiency. Am. J. Med. Genet. (1997) 73:272–275.
   Google Scholar
• LIBBY RT, SMITH RS, SAVINOVA OV et al.: Modification of ocular defects in mouse developmental glaucoma models by tyrosinase. Science (2003) 299:1578–1581.
   Google Scholar
• ••This paper elucidates the underlyingmechanism that links mutation in CYP 1B1 and the development of primary congenital glaucoma. Through understanding the roles played by metabolic enzymes in ocular tissues, mote effective drug therapy may be developed.
   Google Scholar
• ALWARD WL: Biomedicine. A new angle on ocular development. Science (2003) 299:1527–1528.
   Google Scholar
• SCHWARTZMAN ML, MASFERRER J, DUNN MW et al.: Cytochrome P450, drug metabolizing enzymes and arachidonic acid metabolism in bovine ocular tissues. Curt Eye Res. (1987) 6:623–630.
   Google Scholar
• SCHWARTZMAN ML, DAVIS KL, NISHIMURA M et al.: The cytochrome P450 metabolic pathway of arachidonic acid in the cornea. Adv. Prostaglandin Thromboxane Leukot. Res. (1991) 21A:185–192.
   Google Scholar
• ABRAHAM NG, LIN JH, DUNN MW et al.: Presence of haem oxygenase and NADPH cytochrome P450 (c) reductase in human corneal epithelium. Invest. Ophthalmol Vis. Sci. (1987) 28:1464–1472.
   Google Scholar
• SCHWARTZMAN ML, BALAZY M, MASFERRER J et al.: 12 a9-hydroxyicosatetraenoic acid: a cytochrome-P450-dependent arachidonate metabolite that inhibits Nat,K*-ATPase in the cornea. Proc. Natl. Acad. Sci.USA (1987) 84:8125–8129.
   Google Scholar
• MURPHY RC, FALCK JR, LUMIN S et al.: 12 (A)-hydroxyeicosatrienoic acid: a vasodilator cytochrome P450-dependent arachidonate metabolite from the bovine corneal epithelium. J. Biol. Chem. (1988) 263:17197–17202.
   Google Scholar
• MIEYAL PA, DUNN MW, SCHWARTZMAN ML: Detection of endogenous 12-hydroxyeicosatrienoic acid in human tear film. Invest. Ophthalmol Vis. Sci. (2001) 42:328–332.
   Google Scholar
• •Metabolic products from local ocular metabolism can be measured in tears, which may serve as important biomarkers to monitor disease progression and treatment.
   Google Scholar
• DAVIS KL, CONNERS MS, DUNN MW et al: Induction of corneal epithelial cytochrome P450 arachidonate metabolism by contact lens wear. Invest. Ophthalmol. Vis. Sci. (1992) 33:291–297.
   Google Scholar
• VAFEAS C, MIEYAL PA, URBANO F et al.: Hypoxia stimulates the synthesis of cytochrome P450-derived inflammatory eicosanoids in rabbit corneal epithelium. Pharmacol Exp. Ther. (1998) 287:903–910.
   Google Scholar
• ASHKAR S, MESENTSEV A, ZHANG WX et al: Retinoic acid induces corneal epithelial CYP4B1 gene expression and stimulates the synthesis of inflammatory 12-hydroxyeicosanoids. J. Ocul. Pharmacol Ther. (2004) 20:65–74.
   Google Scholar
• BENET LZ, CUMMINS CL, WU CY: Unmasking the dynamic interplay between efflux transporters and metabolic enzymes. Int. J. Pharm. (2004) 277:3–9.
   Google Scholar
• GEORGE RL, HUANG W, NAGGAR HA et al.: Transport of N-acetylaspartate via murine sodium/ dicarboxylate cotransporter NaDC3 and expression of this transporter and aspartoacylase II in ocular tissues in mouse. Biochim. Biophys. Acta (2004) 1690:63–69.
   Google Scholar
• WANG EJ, CASCIANO CN, CLEMENT RP et al: Cooperativity in the inhibition of P-glycoprotein-mediated daunorubicin transport: evidence for half-of-the-sites reactivity. Arch. Biochem. Biophys. (2000) 383:91–98.
   Google Scholar
• DAMM J, RAU T, MAIHOFNER C et al.: Constitutive expression and localization of COX-1 and COX-2 in rabbit iris and ciliary body. Exp. Eye Res. (2001) 72:611–621.
   Google Scholar
• KULKARNI PS, SRINIVASAN BD: Cyclooxygenase and lipoxygenase pathways in anterior uvea and conjunctiva. Prog. Biol. Res. (1989) 312:39–52.
   Google Scholar
• WALTMAN A, SEARS M: Catechol-0-methyl transferase and monoamine oxidase activity in the ocular tissues of albino rabbits. Invest. Ophthalmol (1964) 3:601.
   Google Scholar
• STRATFORD RE LEE VH: Ocular aminopeptidase activity and distribution in the albino rabbit. Curl: Eye Res. (1985) 4:995–999.
   Google Scholar
• STRATFORD RE LEE VH: Aminopeptidase activity in albino rabbit extraocular tissues relative to the small intestine. J. Pharm. Sci. (1985) 74: 731–734.
   Google Scholar
• AZZAROLO AM, BJERRUM K, MAVES CA et al: Hypophysectomy-induced regression of female rat lacrimal glands: partial restoration and maintenance by dihydrotestosterone and prolactin. Invest. Ophthalmol. 1/is. Sci. (1995) 36:216–226.
   Google Scholar
• MIRCHEFF AK, MILLER SS, FARBER DB et al.: Isolation and provisional identification of plasma membrane populations from cultured human retinal pigment epithelium. Invest. Ophthalmol. 1/is. Sci. (1990) 31:863–878.
   Google Scholar
• LI DW- XIANG H, FASS U et al: Analysis of expression patterns of protein phosphatase-1 and phosphatase-2A in rat and bovine lenses. Invest. Ophthalmol. 1/is. ScL (2001) 42:2603–2609.
   Google Scholar
• FEENEY L: Lipofuscin and melanin of human retinal pigment epithelium. Fluorescence, enzyme cytochemical, and ultrastructural studies. Invest. Ophthalmol. 1/is. ScL (1978) 17:583–600.
   Google Scholar
• CABRAL L, UNGER W, BOULTON M et al.: Regional distribution of lysosomal enzymes in the canine retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. (1990) 31:670–676.
   Google Scholar
• HAYASAKA S, SEARS ML: Distribution of acid phosphatase, beta-glucuronidase, and lysosomal hyaluronidase in the anterior segment of the rabbit eye. Invest. Ophthalmol. 1/is. Sci. (1978) 17:982–987.
   Google Scholar
• ROBERTSON MJ, ERWIG LP, LIVERSIDGE J et al.: Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis. Invest. Ophthalmol. 1/is. Sci. (2002) 43:2250–2257.
   Google Scholar
• IKEDA H, UEDA M, IKEDA M et al: Oxysterol ialpha-hydroxylase (CYP39A1) in the ciliary nonpigmented epithelium of bovine eye. Lab. Invest. (2003) 83:349–355.
   Google Scholar
• JAIN-VAKKALAGADDA B, DEY S, PAL D et al.: Identification and functional characterization of a Na'-independent large neutral amino acid transporter, LAT1, in human and rabbit cornea. Invest. Ophthalmol. 1/is. Li. (2003) 44:2919–2927.
   Google Scholar
• MAENPAA H, GEGELASHVILI G, TAHTI H: Expression of glutamate transporter subtypes in cultured retinal pigment epithelial and retinoblastoma cells. Curr. Eye Res. (2004) 28:159–165.
   Google Scholar
• ANAND BS, MITRA AK: Mechanism of corneal permeation of 1-valy1 ester of acyclovir: targeting the oligopeptide transporter on the rabbit cornea. Pharin. Res. (2002) 19:1194–1202.
   Google Scholar
• BASU SK, HAWORTH IS, BOLGER MB et al: Proton-driven dipeptide uptake in primary cultured rabbit conjunctival epithelial cells. Invest. Ophthalmol. 1/is. Li. (1998) 39:2365–2373.
   Google Scholar
• BERGER UV, HEDIGER MA: Distribution of peptide transporter PEPT2 mRNA in the rat nervous system. Anat. Embryo]. (Berlin) (1999) 199:439–449.
   Google Scholar
• BILDIN VN, ISEROVICH P, FISCHBARG J et al.: Differential expression of Na:K:2C1 cotransporter, glucose transporter 1, and aquaporin 1 in freshly isolated and cultured bovine corneal tissues. Exp. Biol. Med. (2001) 226:919–926.
   Google Scholar
• GHERZI R, MELIOLI G, DE LUCA M et al.: High expression levels of the `erythroiclibrain' type glucose transporter (GLUT1) in the basal cells of human eye conjunctiva and oral mucosa reconstituted in culture. Exp. Cell Res. (1991) 195:230–236.
   Google Scholar
• TAKATA K, KASAHARA T, KASAHARA M et al: Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in cells of the blood-retinal barrier in the rat. Invest. Ophthalmol. 1/is. ScL (1992) 33:377–383.
   Google Scholar
• TAKATA K, KASAHARA T, KASAHARA M et al: Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in the ciliary body and iris of the rat eye. Invest. Ophthalmol. 1/is. ScL (1991) 32:1659–1666.
   Google Scholar
• PHILP NJ, WANG D, YOON H et al: Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells. Invest. Ophthalmol. 1/is. ScL (2003) 44:1716–1721.
   Google Scholar