Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC37610.15690/vramn.v69i11-12.1190SHORT MESSAGESКРАТКИЕ СООБЩЕНИЯEXPERIMENTAL MODEL OF OCULAR ISСHEMIC DISEASESЭКСПЕРИМЕНТАЛЬНОЕ МОДЕЛИРОВАНИЕ ИШЕМИЧЕСКОГО ПОРАЖЕНИЯ ГЛАЗАKiselevaT. N.КиселёваТ. Н.
Russian Federation

доктор медицинских наук, профессор, руководитель отделения ультразвука Москов- ского НИИ глазных болезней им. Гельмгольца Адрес: 105062, Москва, ул. Садовая-Черногрязская, д. 14/19, тел.: +7 (495) 624-31-34

tkisseleva@yandex.ruChudinA. V.ЧудинА. В.
Russian Federation

аспирант отдела ультразвука Московского НИИ глазных болезней им. Гельмгольца Адрес: 105062, Москва, ул. Садовая-Черногрязская, д. 14/19, тел.: +7 (495) 624-31-34

ru27@mail.ruHelmholtz Moscow Research Institute of Eye Diseases, Russian FederationМосковский НИИ глазных болезней им. Гельмгольца, Российская Федерация171220146911-12Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук9710307082015Copyright ©; 1970, "Paediatrician" Publishers LLCCopyright ©; 1970, Издательство "Педиатръ"1970"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/376

The review presents the most common methods of modeling of retinal ischemia in vitro (chemical ischemia with iodoacetic acid, incubation of the retinal pigment epithelium cells with oligomycin, deprivation of oxygen and glucose) and in vivo (a model with increased intraocular pressure, cerebral artery occlusion, chronic ligation of the carotid arteries, photocoagulation of the retinal vessels, occlusion of the central retinal artery, endothelin-1 administration). Modeling ischemic injury in rats is the most frequently used method in studies, because the blood supply of their eyes is similar to blood flow in the human eyes. Each method has its own advantages and disadvantages. Application of methods depends on the purpose of the experimental study. Currently model of ocular ischemic disease can be obtained easily by injecting vasoconstrictive drug endothelin-1. It is the most widely used method of high intraocular pressure induced ocular ischemic damage similar to glaucoma, occlusion of central retinal artery or ophthalmic artery in human. The development of experimental models of ocular ischemic diseases and detailed investigation of mechanisms of impairment of microcirculation are useful for improve the efficiency of diagnostic and treatment of ischemic diseases of retina and optic nerve.

В обзоре представлены наиболее распространенные методики моделирования ишемического поражения глаз in vitro (ишемия с использованием йодуксусной кислоты, инкубация клеток ретинального пигментного эпителия с олигомицином, депривация кислорода и глюкозы) и in vivo (модель с повышением внутриглазного давления, окклюзия церебральной артерии, хроническое лигирование сонных артерий, фотокоагуляция ретинальных сосудов, окклюзия центральной артерии сетчатки, введение эндотелина-1). В большинстве экспериментальных исследований используют моделирование ишемического повреждения у крыс, кровоснабжение глаз которых имеет сходство с кровотоком глаза у человека. У каждого метода имеются свои преимущества и недостатки, поэтому их использование напрямую зависит от конкретных целей и задач, которые необходимо решить в ходе экспериментального исследования. В настоящее время легко воспроизводимой моделью ишемического повреждения глаза является субконъюнктивальное введение животным в эксперименте мощного вазоконстриктора эндотелина-1. Наиболее часто используют модель с повышением внутриглазного давления у крыс для воспроизведения ишемических повреждений, аналогичных таковым при глаукоме, окклюзии центральной артерии сетчатки или глазной артерии у человека. Разработка экспериментальных моделей ишемического поражения глаза и более детальное изучение механизмов нарушения кровообращения микрососудистого русла необходимы для повышения эффективности диагностики и лечения ишемического повреждения сетчатки и зрительного нерва.

ischemia-reperfusionexperimental modelretinal ischemiaendothelin-1ишемия-реперфузияэкспериментальная модельретинальная ишемияэндотелин-11. Janáky M., Grósz A., Tóth E., Benedek K., Benedek G. Hypobaric hypoxia reduces the amplitude of oscillatory potentials in the human ERG. Doc. Ophthalmol. 2007; 114 (1): 45–51.2. Tinjust D., Kergoat H., Lovasik J.V. Neuroretinal function during mild systemic hypoxia. Aviat. Space Environ. Med. 2002; 73 (12): 1189–1194.3. Prasad S.S., Kojic L., Wen Y.H., Chen Z., Xiong W., Jia W., Cyander M.S. Retinal gene expression after central retinal artery ligation: effects of ischemia and reperfusion. Inv. Ophthalmol. Vis. Sci. 2010; 51 (12): 6207–6219.4. Kawai S., Vora S., Das S., Gachie E., Becker B., Neufeld A.H. Modeling of risk factors for the degeneration of retinal ganglion cells after ischemia/reperfusion in rats: effects of age, caloric restriction, diabetes, pigmentation and glaucoma. J. FASEB. 2001; 15 (7): 1285–1287.5. Ishihara M., Nakano T., Ohama E., Kawai Y. Postischemic reperfusion in the eyes of young and aged rats. Jpn. J. Physiol. 2000; 50 (1): 125–132.6. Matsuura K., Kawai Y. Effects of hypothermia and aging on postischemic reperfusion in rat eyes. Jpn. J. Physiol. 1998; 48 (1): 9–15.7. Gao G., Li Y., Fant J., Craig E., Crosson S., Becerra P., Ma. J. Difference in ischemic regulation of vascular endothelial growth factor and pigment epithelium-derived factor in Brown Norway and Spargue Dawley rats contributing to different susceptibilities to retinal neovascularisation. Diabetes. 2002; 51 (4): 1218–1255.8. Zhang S.X., Ma J., Sima J., Chen Y., Hu M.S., Ottlecz A., Lambrou G.N. Genetic difference in susceptibility to the blood-retina barrier breakdown in diabetes and oxygen-induced retinopathy. Am. J. Pathol. 2005; 166 (1): 313–321.9. Louzada-Junior P., Dias J.J., Santos W.F., Lachat J.J., Bradford H.F., Goutinho-Netto J. Glutamate release in experimental ischemia of the retina: an approach using microdialysis. J. Neurochemistry. 1992; 59 (1): 358–363.10. Lucas D.R., Newhouse J.P. The toxic effect of sodium L-glutamate on the inner layers of the retina. Arch. Ophthalmology. 1957; 58 (2): 193–201.11. Osborne N.N., Casson R.J., Wood J.P., Chidlow G., Graham M., Melena J. Retinal ischemia: mechanisms of damage and potential therapeutic strategies. Prog. Retin. Eye Res. 2004; 23 (1): 91–147.12. Sims S. R. Energy metabolism and selective neuronal vulnerability following global cerebral ischemia. Neurochemical Research. 1992; 17 (9): 923–931.13. Romano C., Price M.T., Almli T., Olney J.W. Excitotoxic neurodegeneration induced by deprivation of oxygen and glucose in isolated retina. Inv. Ophthalmol. Vis. Sci. 1998; 39 (2): 416–423.14. Ueda K., Makahara T., Hoshino M., Mori A., Sakamoto K. Retinal blood vessels are demaged in rat model of NMDA-induced retinal degeneration. Neurosci. Letters. 2010; 485 (1): 55–59.15. Jennings R.B., Sommers H.M., Smyth G.A., Flack H.A., Linn H. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch. Patholog. 1960; 70: 68–78.16. Krishnamoorthy R.R., Agarwal P., Prasanna G., Vopat K., Lambert W., Sheedlo H.J., Pang I.H., Shade D., Wordinger R.J., Yorio T., Clark A.F., Agarwal N. Characterization of a transformed rat retinal ganglion cell line. Mol. Brain. Res. 2001; 86 (1–2): 1–12.17. Maher P., Hanneken A. Flavonoids protect retinal ganglion cells from ischemia in vitro. Exp. Eye Res. 2008; 86 (2): 366–374.18. Palmero M., Bellor J.L., Castillo M., Garcia-Cabanes C., Miquel J., Orts A. An in vitro model of ischemic like stress in retinal pigmented epithelium cells: protective effects of antioxidants. Mech. Ageing & Dev. 2000; 114 (3): 185–190.19. Romano C., Price M., Bai H.Y., Olney J.W. Neuroprotectants in Honghua: glucose attenuates retinal ischemic damage. Inv. Ophthalmol. Vis. Sci. 1993; 34 (1): 72–80.20. Jung S.H., Kim B.J., Lee E.H., Osborne N.N. Isoquercitrin is the most effective antioxidant in the plant Thuja orientalis and able to counteract oxidative–induced damage to a transformed cell line (RGC-5 cells). Neurochemistry Int. 2010; 57 (7): 713–721.21. Matteuci A., Cammarota R., Paradidi S., Varano M., Balduzzi M., Leo L., Bellenchi G.C., de Nuccio C., Carnovale-Scalzo G., Scorcia G., Frank C., Mallozzi C., di Stasi A.M., Visentin S., Malchiodi-Albedi F. Circumin protects against NMDA-induced toxicity: a possible role for NR2A subunit. Inv. Ophthalmol. Vis. Sci. 2011; 52 (2): 1070–1077.22. Minhas G., Anhad A. Animal models of retinal ischemia. Brain Injury Pathogenesis, Monitoring, Recovery and Management. 2011. URL: http://cdn.intechopen.com/pdfs/34006/ InTechAnimal_models_of_retinal_ischemia.pdf (available: 26.11.1014).23. Flower R.W., Patz A. The effect of hyperbaric oxygenation on retinal ischemia. Inv. Ophthalmol. Vis. Sci. 1971; 10 (8): 605–616.24. Buchi E.R., Suivaizdis I., Fu J. Pressure-induced retinal ischemia in rats: an experimental model for quantitative study. Ophthalmologica. 1991; 203 (3): 138–147.25. Peachey N.S., Green D.J., Ripps H. Ocular ischemia and the effects of allopurinol on functional recovery in the retina of the arterially perfused cat eye. Inv. Ophthalmol. Vis. Sci. 1993; 34 (1): 58–65.26. Osborne N.N., Larsen A.K. Antigens associated with specific retinal cells are affected by ischemia caused by raised intraocular pressure: effect of glutamate antagonists. Neurochem. Int. 1996; 29 (3): 263–270.27. Chidlow G., Schmidt K.G., Wood J.P., Melena J., Osborne N.N. Alpha lipoic acid protects the retina against ischemia-reperfusion. Neuropharmacol. 2002; 43 (6): 1015–1025.28. Joachim S.C., Wax M.B., Boehm N., Dirk D., Pfeiffer N., Grus F.H. Up regulation of antibody response to heat shock proteins and tissue antigens in an ocular ischemia model. Inv. Ophthalmol. Vis. Sci. 2011; 52 (6): 3468–3474.29. Hirrlinger P.G., Elke U., Lanors I., Andreas R., Thomas P. Alterations in protein expression and membrane properties during Muller cell gliosis in a murine model of transient retinal ischemia. Neurosci. Letters. 2010; 472 (1): 73–78.30. Jung S.H., Kang K.D., Ji D., Fawcett R.J., Safa R., Kamalden T.A., Osborne N.N. The flavonoid baicalin counteracts ischemic and pxidative insults to retinal cells and lipid peroxidation to brain membranes. Neurochemistry Int. 2008; 53 (6–8): 325–337.31. Block F., Grommes C., Kosinski C. Retinal ischemia induced by the intraluminal suture methods in rats. Neurosci. Letters. 1997; 232 (1): 45–48.32. Steele E.C., Guo Q., Namura S. Filamentous middle cerebral artery occlusion causes ischemic damage to retina in mice. Stroke. 2008; 39 (7): 2099–2104.33. Kaja S. , Yang S.H., Wei J., Fujitani K., Liu R., Brun-Zinkernagel A.M., Simpkins J.W., Inokuchi K., Koulen P. Estrogen protects the inner retina from apoptosis and ischemia-induced loss of Vesl-1L/Homer-1c immunoreactive synaptic connections. Inv. Ophthalmol. Vis. Sci. 2003; 44 (7): 3155–3162.34. Li X.M., Ma Y.L., Liu X.J. Effect of the Lucium barbarum polysaccharides on age-related oxidative stress in aged mice. J. Ethnopharmacol. 2007; 111 (3): 504–511.35. Block F., Schwarx M., Sontag K.H. Retinal ischemia induced by occlusion of both common carotid arteries in rats as demonstrated by electroretinography. Neurosci. Letters. 1992; 144 (1–2): 124–126.36. Yamamoto H., Schimidt-Kasmer R., Hamasaki D.I., Yamamoto H., Parel J.M. Complex neurodegeneration in retna following moderate ischemia induced by bilateral common carotid artery occlusion in Wistar rats. Exp. Eye Research. 2006; 82 (5): 767–779.37. Barnett N.L., Osborne N.N. Prolonged bilateral carotid artery occlusion induces electrophysiological and immunohistochemical changes to the rat retina without causing histological damage. Exp. Eye Res. 1995; 61 (1): 83–90.38. Davidson C. M., Pappas B. A., Stevens W. D., Fortin T., Bennett S. A. Chronic cerebral hypoperfusion: loss of papillary reflex, visual impairment and retinal neurodegeneration. Brain Res. 2000; 859 (1): 96–103.39. Lavinsky N., Arterni N.S., Achaval M., Netto C.A. Chronic bilateral common carotid artery occlusion: a model for ocular ischemic syndrome in the rat. Arch. Clinic. & Exp. Ophthalmol. 2006; 224 (2): 199–204.40. Atlasz T., Babai N., Reglodi D., Kiss P., Tamas A., Bari F., Domoki F., Gabriel R. Diazoxide is protective in the rat retina against ischemic injury induced by bilateral carotid occlusion and glutamate-induced degeneration. Neur. Res. 2007; 12 (2): 105–111.41. Huang H.M., Huang C.C., Hung P.L., Chang Y.C. Hypoxic-ischemic retinal injury in rat pups. Pediatr. Res. 2012; 72 (3): 224–231.42. Romano C., Price M., Bai H.Y., Olney J.W. Neuroprotectants in Honghua: glucose attenuates retinal ischemic damage. Inv. Ophthalmol. Vis. Sci. 1993; 34 (1): 72–80.43. Miller J.W., Adamis A.P., Shima D.T., D’Amore P.A., Moulton R.S., O’Reilly M.S., Folkman J., Dvorak H.F., Brown L.F., Berse B., Yeo T.-K., Yeot K.-T. Vascular endothelial growth factor/ vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am. J. Pathology. 1994; 145 (3): 574–584.44. Каламкаров Г.Р., Цапенко И.В., Зуева М.В., Иванов А.Н., Резвых С.В., Константинова Т.С., Шевченко Т.Ф. Нитриты способны расширять сосуды при гипоксии и защищать сетчатку от ишемии. Доклады Академии наук. 2007; 417 (2): 263–264.45. Каламкаров Г.Р., Бугрова А.Е., Константинова Т.С., Шевченко Т. Ф., Цапенко И.В., Зуева М.В., Иванов А.Н., Резвых С.В. Протекторное и нейротоксическое действие оксида азота в моделях зрительной патологии. Сборник тезисов по материалам конференции. Под ред. Х.П. Тахчиди. М.: Офтальмология. 2009. С. 541–542.46. Каламкаров Г.Р., Цапенко И.В., Зуева М.В., Иванов А.Н., Константинова Т.С., Бугрова А.Е., Резвых С.В., Федоров А.А., Шевченко Т.Ф. Экспериментальная модель острой ишемии сетчатки глаза у крыс. Бюллетень экспериментальной биологии и медицины. 2008; 6: 634–638.47. Гундорова Р.А., Швецова Н.Е., Иванов А.Н., Цапенко И.В., Федоров А.А., Зуева М.В., Танковский В.Э., Рябина М.В. Модель ишемии сетчатки: клинико-функциональное и гистологическое исследование. Вестник офтальмологии. 2008; 124 (3): 18–22.48. Yuan Y.Z., Yuan F., Xu Q.Y., Yu J., Li L., Zhang J.L. Effect of Fufang Xueshuantong capsule on a rat model of retinal vein occlusion. Chinese J. Int. Med. 2011; 17 (4): 296–301.49. Daugeliene L., Niwa M., Hara A., Matsuno H., Yamamoto T., Kitazawa Y., Uematsu T. Transcient ischemic injury in the rat retina caused by trombotic occlusion-thrombolytic reperfusion. Inv. Ophthalmol. Vis. Sci. 2000; 41 (9): 2743–2747.50. Soga К., Fujita H., Andoh Т., Okumura F. Retinal artery air embolism in dogs: fluorescein angiographic evaluation of effects of hypotension and hemodilution. Anesth. Analg. 1999; 88 (5): 1004–1010.51. Ciulla Т.А., Moulton R., Oberoi A., Miller J.W. Retinal artery occlusion in rabbit eyes using human atheroma. Curr. Eye Res. 1995; 14 (7): 573–578.52. Rubanyi G.M., Polokoff M.A. Endothelins: Molecilar biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol. Rev. 1994; 46: 325–415.53. Syed H., Safa R., Chidlow G., Osborne N.N. Sulfisoxazole, an endothelin receptor antagonist, protects retinal neurons from insults of ischemia/reperfusion or lipopolysaccharide. Neurochemistry Int. 2006; 48 (8): 708–717.54. Takei K., Sato T., Nonoyama T., Miyauchi T., Goto K., Hommura S. A new model of transient complete obstruction of retinal vessels induced by endothelin-1 injection into the posterior vitreous body in rabbits. Arch. Clin. Exp. Ophthalmol. 1993; 231 (8): 476–481.55. Lau J., Dang M., Hockmann K., Ball A.K. Effects of acute delivery of endothelin-1 on retinal ganglion cell loss in the rat. Exp. Eye Res. 2006; 82 (1): 132–145.56. Oku H., Fukuhara M., Kurimoto T., Okuno T., Sugiyama T., Ikeda T. Endothelin-1 (ET-1) is increased in rat retina after crushing optic nerve. Curr. Eye Res. 2008; 33 (7): 611–620.57. Oku H., Fukuhara M., Komori A., Okuno T., Sugiyama T., Ikeda T. Endothelin-1 (ET-1) causes death of retinal neurons through activation of nitric oxide synthase (NOS) and production of superoxide anion. Exp. Eye Res. 2008; 86 (1): 118–130.58. Sugiyama T., Moriya S., Oku H., Azuma I. Association of endothelin-1 with normal tension glaucoma — clinical and fundamental studies. Survey Ophthalmol. 1995; 39 (1): 49–56.59. Granstam E., Wang L., Bill A. Ocular effects of endothelin-1 in the cat. Curr. Eye Res. 1992; 11(4): 325–332.60. Chauhan B.C., LeVatte T.L., Jollimore C.A., Yu P.K., Reitsamer H.A., Kelly M.E., Yu D.Y., Tremblay F., Archibald M.L. Model of endothelin-1-induced chronic optic neuropathy in rat. Inv. Ophthalmol. Vis Sci. 2004; 45 (1): 144–152.61. Masuzawa K., Jesmin S., Maeda S., Kaji Y., Oshika T., Zaedi S., Shimojo N., Yaji N., Miyauchi T., Goto K. A model of retinal ischemia-reperfusion injury in rats by ю. Exp. Biol. Med. (Maywood). 2006; 231 (6): 1085–1089.