Research Progress of ATP-Binding Cassette Efflux Transporters on Blood-Retina Barrier
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摘要: 血-视网膜屏障（BRB）是眼部重要的生物学屏障，能够调节血液和视网膜组织之间的物质交换，防止大分子和其他潜在的有害物质进入视网膜，维持视网膜微环境的稳定。BRB上表达多种外排及摄取转运体，在一些必需营养物质的摄取和神经递质代谢物、激素和药物的外排转运中发挥关键作用。通过对BRB的功能、相关外排转运体的表达和分布以及疾病状态下外排转运体的改变进行综述，以期为治疗视网膜疾病和维持视网膜功能健康的新药研发提供重要信息。Abstract: As an important biological barrier of the eyes, blood-retina barrier(BRB) can regulate the material exchange between blood and retinal tissue, prevent macromolecules and other potentially harmful substances from entering the retina, and maintain the stability of the retinal microenvironment.It can express a variety of efflux and uptake transporters, which play a key role in the uptake of some essential nutrients and the efflux of neurotransmitter metabolites, hormones and drugs.This paper describes the function of BRB, the expression and distribution of related efflux transporters, and the changes of efflux transporters in disease states, providing important information for the development of new drugs for the treatment of retinal diseases and the maintenance of retinal functional health.
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[1] 唐仕波, 唐细兰.眼科药物治疗学[M].北京:人民卫生出版社, 2010. [2] 陈祖基.重视眼部给药系统的研究[J].中华眼科杂志, 2006, 42(4):292-295. [3] Hosoya K, Tomi M, Tachikawa M.Strategies for therapy of retinal diseases using systemic drug delivery:relevance of transporters at the blood-retinal barrier[J].Expert Opin Drug Deliv, 2011, 8(12):1571-1587.
[4] Li M S, Xin M, Guo C L, et al.Differential expression of breast cancer-resistance protein, lung resistance protein, and multidrug resistance protein 1 in retinas of streptozotocin-induced diabetic mice[J].Int J Ophthalmol, 2017, 10(4):515-523.
[5] Benezra D, Maftzir G.Ocular penetration of cyclosporine A in the rat eye[J].Arch Ophthalmol, 1990, 108(4):584-587.
[6] Mannermaa E, Vellonen K S, Urtti A.Drug transport in corneal epithelium and blood-retina barrier:emerging role of transporters in ocular pharmacokinetics[J].Adv Drug Deliv Rev, 2006, 58(11):1136-1163.
[7] Mao Q C, Unadkat J D.Role of the breast cancer resistance protein(BCRP/ABCG2) in drug transport-an update[J].AAPS J, 2015, 17(1):65-82.
[8] Díaz-Coránguez M, Ramos C, Antonetti D A.The inner blood-retinal barrier:cellular basis and development[J/OL].Vision Res, 2017, 139:123-137[2021-02-05].https://doi.org/10.1016/j.visres.2017.05.009.
[9] Hosoya K, Tachikawa M.Inner blood-retinal barrier transporters:role of retinal drug delivery[J].Pharm Res, 2009, 26(9):2055-2065.
[10] Tomi M, Hosoya K.The role of blood-ocular barrier transporters in retinal drug disposition:an overview[J].Expert Opin Drug Metab Toxicol, 2010, 6(9):1111-1124.
[11] Ganapathy V, Thangaraju M, Gopal E, et al.Sodium-coupled monocarboxylate transporters in normal tissues and in cancer[J].AAPS J, 2008, 10(1):193-199.
[12] Mollazadeh S, Sahebkar A, Hadizadeh F, et al.Structural and functional aspects of P-glycoprotein and its inhibitors[J/OL].Life Sci, 2018, 214:118-123[2021-02-05].https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(18)30673-8.DOI: 10.1016/j.lfs.2018.10.048.
[13] Sharom F J.ABC multidrug transporters:structure, function and role in chemoresistance[J].Pharmacogenomics, 2008, 9(1):105-127.
[14] Tsuji A.Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems[J].Neuro Rx, 2005, 2(1):54-62.
[15] Tsuji A, Terasaki T, Takabatake Y, et al.P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells[J].Life Sci, 1992, 51(18):1427-1437.
[16] Shen J, Cross S T, Tang-Liu D D S, et al.Evaluation of an immortalized retinal endothelial cell line as an in vitro model for drug transport studies across the blood-retinal barrier[J].Pharm Res, 2003, 20(9):1357-1363.
[18] Zhang T, Xiang C D, Gale D, et al.Drug transporter and cytochrome P450 m RNA expression in human ocular barriers:implications for ocular drug disposition[J].Drug Metab Dispos, 2008, 36(7):1300-1307.
[19] Wu J, Zhang J J, Koppel H, et al.P-glycoprotein regulates a volume-activated chloride current in bovine non-pigmented ciliary epithelial cells[J].J Physiol, 1996, 491 (Pt3):743-755.
[20] Chapy H, Saubaméa B, Tournier N, et al.Blood-brain and retinal barriers show dissimilar ABC transporter impacts and concealed effect of P-glycoprotein on a novel verapamil influx carrier[J].Br Jpharmacol, 2016, 173(3):497-510.
[21] Zhang Y H, Li J, Yang W Z, et al.Mitochondrial expression and activity of P-glycoprotein under oxidative stress in outer bloodretinal barrier[J].Int J Ophthalmol, 2017, 10(7):1055-1063.
[22] 陈翀, 许迅.血-视网膜屏障转运载体的研究进展[J].中华实验眼科杂志, 2015, 33(12):1131-1137. [23] Liu L, Liu X D.Roles of drug transporters in blood-retinal barrier[J/OL].Adv Exp Med Biol, 2019, 1141:467-504[2021-02-05].https://link.springer.com/chapter/10.1007%2F978-981-13-7647-4_10.DOI: 10.1007/978-981-13-7647-4_10.
[24] Benezra D, Maftzir G.Ocular penetration of cyclosporin A.The rabbit eye[J].Invest Ophthalmol Vis Sci, 1990, 31(7):1362-1366.
[25] Diop N K, Hrycyna C A.N-linked glycosylation of the human ABC transporter ABCG2 on asparagine 596 is not essential for expression, transport activity, or trafficking to the plasma membrane[J].Biochemistry, 2005, 44(14):5420-5429.
[26] Pelkonen L, Sato K, Reinisalo M, et al.LC-MS/MS based quantitation of ABC and SLC transporter proteins in plasma membranes of cultured primary human retinal pigment epithelium cells and immortalized ARPE19 cell line[J].Mol Pharm, 2017, 14(3):605-613.
[27] Zhang Z, Uchida Y, Hirano S, et al.Inner blood-retinal barrier dominantly expresses breast cancer resistance protein:comparative quantitative targeted absolute proteomics study of CNS barriers in pig[J].Mol Pharm, 2017, 14(11):3729-3738.
[28] Mannermaa E, Vellonen K S, Ryhänen T, et al.Efflux protein expression in human retinal pigment epithelium cell lines[J].Pharm Res, 2009, 26(7):1785-1791.
[29] Vellonen K S, Hellinen L, Mannermaa E, et al.Expression, activity and pharmacokinetic impact of ocular transporters[J/OL].Adv Drug Deliv Rev, 2018, 126:3-22[2021-02-05].https://linkinghub.elsevier.com/retrieve/pii/S0169-409X(17)30312-5.DOI: 10.1016/j.addr.2017.12.009.
[30] Asashima T, Hori S, Ohtsuki S, et al.ATP-binding cassette transporter G2 mediates the efflux of phototoxins on the luminal membrane of retinal capillary endothelial cells[J].Pharm Res, 2006, 23(6):1235-1242.
[31] Hipfner D R, Almquist K C, Leslie E M, et al.Membrane topology of the multidrug resistance protein (MRP).A study of glycosylationsite mutants reveals an extracytosolic NH2 terminus[J].J Biol Chem, 1997, 272(38):23623-23630.
[32] Tachikawa M, Toki H, Tomi M, et al.Gene expression profiles of ATP-binding cassette transporter A and C subfamilies in mouse retinal vascular endothelial cells[J].Microvasc Res, 2008, 75(1):68-72.
[33] Tagami M, Kusuhara S, Honda S, et al.Expression of ATP-binding cassette transporters at the inner blood-retinal barrier in a neonatal mouse model of oxygen-induced retinopathy[J/OL].Brain Res, 2009, 1283:186-193[2021-02-05].https://doi.org/10.1016/j.addr.2017.12.009.
[34] Aukunuru J V, Sunkara G, Bandi N, et al.Expression of multidrug resistance-associated protein (MRP) in human retinal pigment epithelial cells and its interaction with BAPSG, a novel aldose reductase inhibitor[J].Pharm Res, 2001, 18(5):565-572.
[35] Blair N P, Rusin M M.Blood-retinal barrier permeability to carboxyfluorescein and fluorescein in monkeys[J].Graefes Arch Clin Exp Ophthalmol, 1986, 224(5):419-422.
[36] Cunha-Vaz J G, Maurice D M.The active transport of fluorescein by the retinal vessels and the retina[J].J Physiol, 1967, 191(3):467-486.
[37] Oguro Y, Tsukahara Y, Saito I, et al.Estimation of the permeability of the blood-retinal barrier in normal individuals[J].Invest Ophthalmol Vis Sci, 1985, 26(7):969-976.
[38] Steuer H, Jaworski A, Elger B, et al.Functional characterization and comparison of the outer blood-retina barrier and the blood-brain barrier[J].Invest Ophthalmol Vis Sci, 2005, 46(3):1047-1053.
[39] Deissler H L, Lang G K, Lang G E.Capacity of aflibercept to counteract VEGF-stimulated abnormal behavior of retinal microvascular endothelial cells[J/OL].Exp Eye Res, 2014, 122:20-31[2021-02-05].https://doi.org/10.1016/j.exer.2014.02.024.
[40] Lin Y X, Bircsak K M, Gorczyca L, et al.Regulation of the placental BCRP transporter by PPAR gamma[J/OL].J Biochem Mol Toxicol, 2017, 31(5):10.1002/jbt.21880[2021-02-05].https://doi.org/10.1002/jbt.21880.
[41] Sreekumar P G, Spee C, Ryan S J, et al.Mechanism of RPEcell death inα-crystallin deficient mice:a novel and critical role for MRP1-mediated GSH efflux[J].PLo S One, 2012, 7(3):e33420[2021-02-05].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307734/.DOI: 10.1371/journal.pone.0033420.
[42] Barakat S, Turcotte S, Demeule M, et al.Regulation of brain endothelial cells migration and angiogenesis by P-glycoprotein/caveolin-1 interaction[J].Biochem Biophys Res Commun, 2008, 372(3):440-446.
[43] Sene A, Khan A A, Cox D, et al.Impaired cholesterol efflux in senescent macrophages promotes age-relatedmacular degeneration[J].Cell Metab, 2013, 17(4):549-561.
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