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近年来,人们不断从形态结构、生理生化、病理改变等各个方面对视网膜进行着探索,其研究方法主要有苏木精-伊红染色等形态学研究、酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组化研究、基因研究等。随着核医学显像技术的不断发展,核医学视网膜受体显像也取得了很大进展。本文就视网膜内的各种神经递质及其核医学分子显像进行综述。
视网膜神经受体及其分子显像研究进展
Review of retinal receptors and molecular imaging
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摘要: 视网膜的合成、代谢等各项生理功能主要是由视网膜内的神经递质(谷氨酸、γ-氨基丁酸、多巴胺、5-羟色胺、σ受体等)协同作用完成。近年来核医学显像仪器及显像剂的蓬勃发展促进了全身各器官系统功能的分子水平研究,视网膜受体分子显像是将核医学、眼科学、分子生物学相结合的新医学技术,是当前核医学研究领域的一个开拓性的新进展。笔者将从视网膜内的各种神经递质的生理病理变化及其在核医学分子显像领域的研究进行综述。Abstract: Retinal synthetic functions are adjusted by various neurotransmitters(e.g., γ-aminobutyric acid, dopamine, 5 -hydroxytryptamine, and σ receptor) and can be visualized through nuclear receptor imaging. This technology has rapidly advanced in recent years with the development of nuclear medical equipment and agents. Retinal receptor imaging has become a pioneer medical technique that combines molecular biology, nuclear medicine, and ophthalmology. This article provides a brief introduction on the latest advances in retinal neurotransmitters and describes recent studies on retinal receptor molecular imaging.
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Key words:
- Retina /
- Receptor, dopamine /
- Dopamine transporter /
- 5-hydroxytryptamine /
- σreceptor /
- Positron-emission tomography
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[1] De Melo Reis RA, Cabral-Da-Silva Me, De Mello FG, et al.Müller glia factors induce survival and neuritogenesis of peripheral and central neurons[J]. Brain Res, 2008, 1205:1-11. DOI:10.1016/j.brainres.2008.02.035. [2] Kubrusly RC, Panizzutti R, Gardino PF, et al. Expression of functional dopaminergic phenotype in purified cultured muller cells from vertebrate retina[J]. Neurochem Int, 2008, 53(3/4):63-70. DOI:10.1016/j.neuint.2008.05.002. [3] Semkova I, Huemmeke M, Ho MS, et al. Retinal localization of the glutamate receptor GluR2 and GluR2-regulating proteins in diabetic rats[J]. Exp Eye Res, 2010, 90(2):244-253. DOI:10.1016/j.exer.2009.10.012. [4] Gu L, Xu H, Wang F, et al. Erythropoietin exerts a neuroprotective function against glutamate neurotoxicity in experimental diabetic retina[J]. Invest Ophthalmol Vis Sci, 2014, 55(12):8208-8222. DOI:10.1167/iovs.14-14435. [5] Belforte NA, Moreno MC, De Zavalía N, et al. Melatonin:a novel neuroprotectant for the treatment of glaucoma[J]. J Pineal Res, 2010, 48(4):353-364. DOI:10.1111/j.1600-079X.2010.00762.x. [6] 王中峰, 杨雄里.谷氨酸受体在实验性青光眼视网膜细胞损伤中的作用[J].生理学报, 2016, 68(4):483-491.
Wang ZF, Yang XL. Glutamate receptor-mediated retinal neuronal injury in experimental glaucoma[J]. Acta Physiol Sin, 2016, 68(4):483-491.[7] Santiago AR, Hughes JM, Kamphuis W, et al. Diabetes changes ionotropic glutamate receptor subunit expression level in the human retina[J]. Brain Res, 2008, 1198:153-159. DOI:10.1016/j.brainres.2007.12.030. [8] Fu S, Dong S, Zhu M, et al. Müller Glia are a major cellular source of survival signals for retinal neurons in diabetes[J]. Diabetes, 2015, 64(10):3554-3563. DOI:10.2337/db15-0180. [9] Akopian A, Kumar S, Ramakrishnan H, et al. Amacrine cells coupled to ganglion cells via gap junctions are highly vulnerable in glaucomatous mouse retinas[J/OL]. J Comp Neurol, 2016[2017-06-20]. http://onlinelibrary.wiley.com/doi/10.1002/cne.24074/abstract.[Epublished online ahead of print July 25, 2016]. DOI:10.1002/cne.24074. [10] Sanchez-Chavez G, Velazquez-Flores MA, Ruiz ER, et al. Glycine receptor subunits expression in the developing rat retina[J]. Neuro-chem Int, 2017, 108:177-182. DOI:10.1016/j.neuint.2017.03.013. [11] Zhou X, Pardue MT, Iuvone PM, et al. Dopamine signaling and myopia development:What are the key challenges[J/OL]. Prog Retin Eye Res, 2017[2017-06-20]. https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(17)30010-1.DOI:10.1016/j.preteyeres.2017.06.003. [12] Yang JW, Xu YC, Sun L, et al. 5-hydroxytryptamine level and 5-HT2A receptor mRNA expression in the guinea pigs eyes with spectacle lens-induced myopia[J]. Int J Ophthalmol, 2010, 3(4):299-303. DOI:10.3980/j.issn.2222-3959.2010.04.05. [13] Wang WF, Ishiwata K, Kiyosawa M, et al. Investigation of the use of positron emission tomography for neuroreceptor imaging in rabbit eyes[J]. Ophthalmic Res, 2004, 36(5):255-263. DOI:10.1159/000081205. [14] Malmfors T. Evidence of adrenergic neurons with synaptic terminals in the retina of rats demonstrated with fluorescence and electron microscopy[J]. Acta Physiol Scand, 1963, 58(1):99-100. DOI:10.1111/j.1748-1716.1963.tb02632.x. [15] Nickla DL, Totonelly K, Dhillon B. Dopaminergic agonists that result in ocular growth inhibition also elicit transient increases in choroidal thickness in chicks[J]. Exp Eye Res, 2010, 91(5):715-720. DOI:10.1016/j.exer.2010.08.021. [16] Huang F, Yan T, Shi F, et al. Activation of dopamine D2 receptor is critical for the development of form-deprivation myopia in the C57BL/6 mouse[J]. Invest Ophthalmol Vis Sci, 2014, 55(9):5537-5544. DOI:10.1167/iovs.13-13211. [17] Ward AH, Siegwart JT, Frost MR, et al. Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews[J/OL]. Vis Neurosci, 2017, 34:E003[2017-06-20]. https://www.cambridge.org/core/journals/visual-neuroscience/article/intravitreallyadministered-dopamine-d2like-and-d4-but-not-d1like-receptor-agonists-reduce-formdeprivation-myopia-in-tree-shrews/48D706C13ED5DB116BA32E9646D9FCD3.DOI:10.1017/S0952523816000195. [18] 赵娟, 刘兴党.实验性近视眼视网膜多巴胺神经系统研究进展[J].国际放射医学核医学杂志, 2007, 31(2):73-76. DOI:10.3760/cma.j.issn.1673-4114.2007.02.004.
Zhao J, Liu XD. Study and development of retinal dopamine nervous system in experimental myopia[J]. Int J Radiat Med Nucl Med, 2007, 31(2):73-76. doi: 10.3760/cma.j.issn.1673-4114.2007.02.004[19] Lacivita E, De Giorgio P, Lee IT, et al. Design, synthesis, radiolabeling, and in vivo evaluation of carbon-11 labeled N-[2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a potential positron emission tomography tracer for the dopamine D(4) receptors[J]. J Med Chem, 2010, 53(20):7344-7355. DOI:10.1021/jm100925m. [20] 毛俊峰, 刘双珍, 秦文娟, 等.豚鼠形觉剥夺性近视眼视网膜, 脉络膜多巴胺代谢的变化[J].中华眼视光学与视觉科学杂志, 2009, 11(1):33-37. DOI:10.3760/cma.j.issn.1674-845X.2009.01.010.
Mao JF, Liu SZ, Qin WJ, et al. The change in dopamine metabolism in the retina and choroid of the Guinea pig with form-deprivation myopia[J]. Chin J Optom Ophthalmol Vis Sci, 2009, 11(1):33-37. doi: 10.3760/cma.j.issn.1674-845X.2009.01.010[21] Stone RA, Cohen Y, Mcglinn AM, et al. Development of experimental myopia in chicks in a natural environment[J]. Invest Ophthalmol Vis Sci, 2016, 57(11):4779-4789. DOI:10.1167/iovs.16-19310. [22] Zhao J, Qu X, Qi Y, et al. Study on retinal dopamine transporter in form deprivation myopia using the radiopharmaceutical tracer 99mTc-TRODAT-1[J]. Nucl Med Commun, 2010, 31(10):910-915. DOI:10.1097/MNM.0b013e32833decc0. [23] Tuerxun T, Numakawa T, Adachi N, et al. SA4503, a sigma-1 receptor agonist, prevents cultured cortical neurons from oxidative stressinduced cell death via suppression of MAPK pathway activation and glutamate receptor expression[J]. Neurosci Lett, 2010, 469(3):303-308. DOI:10.1016/j.neulet.2009.12.013. [24] Chien CC, Pasternak GW. Selective antagonism of opioid analgesia by a sigma system[J]. J Pharmacol Exp Ther, 1994, 271(3):1583-1590. [25] Ramakrishnan NK, Visser AK, Schepers M, et al. Dose-dependent sigma-1 receptor occupancy by donepezil in rat brain can be assessed with 11C-SA4503 and microPET[J]. Psychopharmacology(Berl), 2014, 231(20):3997-4006. DOI:10.1007/s00213-014-3533-2. [26] Liu LL, Wang L, Zhong YM, et al. Expression of sigma receptor 1 mRNA and protein in rat retina[J]. Neuroscience, 2010, 167(4):1151-1159. DOI:10.1016/j.neuroscience.2010.03.006. [27] Tagashira H, Zhang C, Lu YM, et al. Stimulation of sigma-1 receptor restores abnormal mitochondrial Ca2+ mobilization and ATP production following cardiac hypertrophy[J]. Biochim Biophys Acta, 2013, 1830(4):3082-3094. DOI:10.1016/j.bbagen.2012.12.029. [28] Shimazawa M, Sugitani S, Inoue Y, et al. Effect of a sigma-1 receptor agonist, cutamesine dihydrochloride (SA4503), on photoreceptor cell death against light-induced damage[J]. Exp Eye Res, 2015, 132:64-72. DOI:10.1016/j.exer.2015.01.017. [29] Vilner BJ, John CS, Bowen WD. Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines[J]. Cancer Res, 1995, 55(2):408-413. [30] Wang WF, Ishiwata K, Kiyosawa M, et al. Visualization of sigma1 receptors in eyes by ex vivo autoradiography and in vivo positron emission tomography[J]. Exp Eye Res, 2002, 75(6):723-730. doi: 10.1006/exer.2002.2048 [31] Bor-Seng-Shu E, Felicio AC, Braga-Neto P, et al. Dopamine transporter imaging using 99mTc-TRODAT-1 SPECT in Parkinson's disease[J]. Med Sci Monit, 2014, 20:1413-1418. DOI:10.12659/MSM.890522. [32] Shimizu S, Hirao K, Kanetaka H, et al. Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimer's disease[J]. Eur J Nucl Med Mol Imaging, 2016, 43(1):184-192. DOI:10.1007/s00259-015-3146-y. [33] Wu H, Lou C, Huang Z, et al. SPECT imaging of dopamine transporters with 99mTc-TRODAT-1 in major depression and Parkinson's disease[J]. J Neuropsychiatry Clin Neurosci, 2011, 23(1):63-67. DOI:10.1176/jnp.23.1.jnp63. [34] Yuan J, Liu XD, Han M, et al. Comparison of striatal dopamine transporter levels in chronic heroin-dependent and methamphetamine-dependent subjects[J]. Addict Biol, 2015, 22(1):229-234. DOI:10.1111/adb.12271. [35] Yuan J, Lv R, Robert Brašić J, et al. Dopamine transporter dysfunction in Han Chinese people with chronic methamphetamine dependence after a short-term abstinence[J]. Psychiatry Res, 2014, 221(1):92-96. DOI:10.1016/j.pscychresns.2013.11.005. [36] Liu Y, Han M, Liu X, et al. Dopamine transporter availability in heroin-dependent subjects and controls:longitudinal changes during abstinence and the effects of Jitai tablets treatment[J]. Psychopharmacology(Berl), 2013, 230(2):235-244. DOI:10.1007/s00213-013-3148-z. [37] 席晓勍, 褚仁远, 周行涛, 等.实验性近视眼视网膜多巴胺转运蛋白研究[J].中华眼科杂志, 2003, 39(6):27-30. DOI:10.3760/j:issn:0412-4081.2003.06.007.
Xi XQ, Chu RY, Zhou HT, et al. Studies of retinal dopamine transporter in experimental myopia[J]. Chin J Ophthalmol, 2003, 39(6):27-30. doi: 10.3760/j:issn:0412-4081.2003.06.007[38] 汪维芳, 盛敏杰, 林安娟, 等.正电子发射断层扫描术在兔眼神经受体成像的应用[J].眼科新进展, 2009, 29(7):514-518.
Wang WF, Sheng MJ, Lin AJ, et al. Application of positron emission tomography for imaging of neuroreceptor in rabbit eyes[J]. Rec Adv Ophthal, 2009, 29(7):514-518.[39] 汪维芳, 盛敏杰, 林安娟, 等.眼内σ1受体在PET中显像的实验研究[J].眼科, 2009, 18(3):198-203.
Wang WF, Sheng MJ, Lin AJ, et al. Visualization of σ1 receptors in eyes by in vivo positron emission tomography and ex vivo autoradiography[J]. Ophthalmol Chn, 2009, 18(3):198-203.
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