<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">helmholtzeyeinstitute</journal-id><journal-title-group><journal-title xml:lang="ru">Российский офтальмологический журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Russian Ophthalmological Journal</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2072-0076</issn><issn pub-type="epub">2587-5760</issn><publisher><publisher-name>Real time Publishers</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21516/2072-0076-2022-15-3-118-122</article-id><article-id custom-type="elpub" pub-id-type="custom">helmholtzeyeinstitute-1059</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ЭКСПЕРИМЕНТАЛЬНО-ЛАБОРАТОРНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>EXPERIMENTAL AND LABORATORY STUDIES</subject></subj-group></article-categories><title-group><article-title>Экспериментальное обоснование местного применения ингибиторов ангиотензинпревращающего фермента в виде глазных капель при ишемических процессах в глазу</article-title><trans-title-group xml:lang="en"><trans-title>Experimental evidence for the topical use of angiotensin-converting enzyme inhibitors in eye drops for eye ischemia treatment</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чеснокова</surname><given-names>Н. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Chesnokova</surname><given-names>N. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Наталья Борисовна Чеснокова – доктор биологических наук, профессор, главный специалист отдела патофизиологии и биохимии.</p><p>Ул. Садовая-Черногрязская, д. 14/19, Москва, 105062</p></bio><bio xml:lang="en"><p>Natalya B. Chesnokova — Dr. of Biol. Sci., professor, chief specialist, department of pathophysiology and biochemistry.</p><p>14/19, Sadovaya-Chernogriazskaya St., Moscow, 105062</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кост</surname><given-names>О. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kost</surname><given-names>O. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ольга Алексеевна Кост — ведущий научный сотрудник кафедры химической энзимологии.</p><p>Ленинские горы, д. 1, Москва, 119991</p></bio><bio xml:lang="en"><p>Olga A. Kost — Cand. of Chem. Sci., leading researcher, department of chemical enzymology.</p><p>GSP-1, 1, Leninskie Gory, Moscow, 119991</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Безнос</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Beznos</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ольга Валерьевна Безнос — научный сотрудник отдела патофизиологии и биохимии.</p><p>Ул. Садовая-Черногрязская, д. 14/19, Москва, 105062</p></bio><bio xml:lang="en"><p>Olga V. Beznos — researcher, department of pathophysiology and biochemistry.</p><p>14/19, Sadovaya-Chernogriazskaya St., Moscow, 105062</p></bio><email xlink:type="simple">olval2011@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Григорьев</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Grigoryev</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Андрей Владимирович Григорьев — кандидат медицинских наук, зав. клинико-диагностической лабораторией.</p><p>Ул. Садовая-Черногрязская, д. 14/19, Москва, 105062</p></bio><bio xml:lang="en"><p>Andrey V. Grigoryev — Cand. of Med. Sci., head of clinical diagnostic laboratory.</p><p>14/19, Sadovaya-Chernogriazskaya St., Moscow, 105062</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Биневский</surname><given-names>П. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Binevski</surname><given-names>P. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Петр Витальевич Биневский — кандидат химических наук, старший научный сотрудник кафедры химической энзимологии.</p><p>Ленинские горы, д. 1, Москва, 119991</p></bio><bio xml:lang="en"><p>Peter V. Binevski — Cand. of Chem. Sci., senior researcher, department of chemical enzymology.</p><p>GSP-1, 1, Leninskie Gory, Moscow, 119991</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Павленко</surname><given-names>Т. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Pavlenko</surname><given-names>T. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Татьяна Аркадьевна Павленко — кандидат медицинских наук, начальник отдела патофизиологии и биохимии ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»,</p><p>Ленинские горы, д. 1, Москва, 119991</p></bio><bio xml:lang="en"><p>Tatyana A. Pavlenko — Cand. of Med. Sci., head of the department of pathophysiology and biochemistry.</p><p>14/19, Sadovaya-Chernogriazskaya St., Moscow, 105062</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ «НМИЦ глазных болезней им. Гельмгольца» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Helmholtz National Medical Research Center of Eye Diseases</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Moscow State University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>23</day><month>09</month><year>2022</year></pub-date><volume>15</volume><issue>3</issue><fpage>118</fpage><lpage>122</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Чеснокова Н.Б., Кост О.А., Безнос О.В., Григорьев А.В., Биневский П.В., Павленко Т.А., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Чеснокова Н.Б., Кост О.А., Безнос О.В., Григорьев А.В., Биневский П.В., Павленко Т.А.</copyright-holder><copyright-holder xml:lang="en">Chesnokova N.B., Kost O.A., Beznos O.V., Grigoryev A.V., Binevski P.V., Pavlenko T.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://roj.igb.ru/jour/article/view/1059">https://roj.igb.ru/jour/article/view/1059</self-uri><abstract><p>Цель работы — оценить влияние местного применения ингибитора ангиотензинпревращающего фермента (иАПФ) эналаприлата в виде глазных капель на интенсивность кровотока в сосудах глаза, выраженность гипоксии, активность АПФ и общую антиоксидантную активность (АОА) в водянистой влаге кроликов с экспериментальной ишемией глаза.</p><sec><title>Материал и методы</title><p>Материал и методы. Транзиторную ишемию глаза у 30 кроликов породы шиншилла воспроизводили путем субконъюнктивального введения 0,2 мл 1 % фенилэфрина. Степень выраженности ишемии оценивали по величине минутного объема кровотока (МОК), который определяли с помощью офтальмоплетизмографии. Эналаприлат 0,125 % применяли в виде инстилляций. Активность АПФ в водянистой влаге измеряли спектрофлюорометрическим методом со специфическим субстратом 0,1 мМ Z-Phe-His-Leu. Выраженность гипоксии оценивали по уровню лактата в водянистой влаге, который измеряли ферментативным амперометрическим методом. Уровень АОА определяли путем регистрации кинетики хемилюминесценции в модельной системе «гемоглобин — Н2О2 — люминол».</p></sec><sec><title>Результаты</title><p>Результаты. Однократная инстилляция иАПФ в здоровый интактный глаз кролика вызывает уменьшение МОК и активности АПФ в водянистой влаге. При ишемии активность АПФ и уровень лактата в водянистой влаге увеличиваются, в то время как АОА снижается. Инстилляция иАПФ на фоне ишемии приводит к нормализации МОК, активности АПФ, концентрации лактата и АОА в водянистой влаге.</p></sec><sec><title>Заключение</title><p>Заключение. При инстилляционном способе введения иАПФ способны проникать во внутренние структуры глаза. Инстилляция иАПФ на фоне ишемии глаза вызывают значительное увеличение глазного кровотока и снижение повышенной при ишемии активности АПФ во внутриглазной жидкости. Противоишемический эффект иАПФ сопровождается антигипоксическим и антиоксидантным действием. Таким образом, иАПФ в виде глазных капель могут найти применение в офтальмологии в качестве противоишемического средства.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Purpose</title><p>Purpose: to evaluate the topical use effect of angiotensin-converting enzyme (ACE) inhibitor (iACE) Enalaprilat in eye drops on eye blood flow volume, hypoxia degree, ACE activity, and total antioxidant activity (TAA) in aqueous humor of rabbits with experimental ocular ischemia.</p></sec><sec><title>Material and methods</title><p>Material and methods. Transient ocular ischemia in 30 Chinchilla rabbits was induced by subconjunctivally injecting 0.2 ml of 1 % Phenylephrine. Ocular ischemia degree was assessed by the minute volume of blood flow (MBF), determined with the help of ophthalmic plethysmography. 0.125 % Enalaprilat was administered by instillations. A CE activity in aqueous humor was measured using a spectrofluorometric assay with 0.1 mM Z-Phe-His-Leu substrate; the degree of hypoxia was estimated by the level of lactate in aqueous humor, which was determined by the enzymatic amperometric method. TAA was determined by registering chemiluminescence kinetics in the hemoglobin-H2O2-luminol model system.</p></sec><sec><title>Results</title><p>Results. A single instillation of iACE in the intact rabbit eye caused a decline of MBF value and A CE activity in aqueous humor. In ocular ischemia, ACE activity and t he lactate level in aqueous humor are increasing, while TAA is decreasing. Enalaprilat instillation in the eyes with ischemia lead to the normalization of MBF, ACE activity, lactate level and TAA in aqueous humor.</p></sec><sec><title>Conclusion</title><p>Conclusion. Topical iACE in eye drops can penetrate eye tissues. Instillations of iACE during ischemia cause a remarkable increase of eye blood flow and reduce ACE activity, which is increased in ischemia. The anti-ischemic effect of iACE is accompanied by antihypoxant and antioxidant effects. Thus, iACE in eye drops can be used in ophthalmology as an anti-ischemic agent.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>ангиотензинпревращающий фермент</kwd><kwd>ингибиторы ангиотензинпревращающего фермента</kwd><kwd>гипоксия</kwd><kwd>ишемия глаза</kwd><kwd>водянистая влага</kwd><kwd>антиоксидантная активность</kwd><kwd>лактат</kwd><kwd>офтальмоплетизмография</kwd></kwd-group><kwd-group xml:lang="en"><kwd>angiotensin-converting enzyme</kwd><kwd>angiotensin-converting enzyme inhibitors</kwd><kwd>hypoxia</kwd><kwd>ocular ischemia</kwd><kwd>aqueous humor</kwd><kwd>antioxidant activity</kwd><kwd>lactate</kwd><kwd>ophthalmic plethysmography</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Rivera J.C., Dabouz R., Noueihed B., et al. Ischemic retinopathies: oxidative stress and inflammation. Oxid. Med. Cell. Longev. 2017; 2017: 3940241. doi: 10.1155/2017/3940241</mixed-citation><mixed-citation xml:lang="en">Rivera J.C., Dabouz R., Noueihed B., et al. Ischemic retinopathies: oxidative stress and inflammation. Oxid. Med. Cell. Longev. 2017; 2017: 3940241. doi: 10.1155/2017/3940241</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Terelak-Borys B., Skonieczna K., Grabska-Liberek I. Ocular ischemic syndrome -a systematic review. Med. Sci. Monit. 2012; 18 (8): RA138-44. doi: 10.12659/msm.883260</mixed-citation><mixed-citation xml:lang="en">Terelak-Borys B., Skonieczna K., Grabska-Liberek I. Ocular ischemic syndrome -a systematic review. Med. Sci. Monit. 2012; 18 (8): RA138-44. doi: 10.12659/msm.883260</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Aouiss A., Idrissi A.D., Kabine M., Zaid Y. Update of inflammatory proliferative retinopathy: Ischemia, hypoxia and angiogenesis. Curr. Res. Transl. Med. 2019; 61 (2): 62-71. doi:10.1016/j.retram.2019.01.0</mixed-citation><mixed-citation xml:lang="en">Aouiss A., Idrissi A.D., Kabine M., Zaid Y. Update of inflammatory proliferative retinopathy: Ischemia, hypoxia and angiogenesis. Curr. Res. Transl. Med. 2019; 61 (2): 62-71. doi:10.1016/j.retram.2019.01.0</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Sturrock E.D., Anthony S., Danilov S.M. Peptidyl-dipeptidase A/angiotensin I-converting enzyme. In: Rawlings N.D., Salvesen G., eds. Handbook of Proteolytic Enzymes, 3d ed. Oxford: Academic Press; 2012.</mixed-citation><mixed-citation xml:lang="en">Sturrock E.D., Anthony S., Danilov S.M. Peptidyl-dipeptidase A/angiotensin I-converting enzyme. In: Rawlings N.D., Salvesen G., eds. Handbook of Proteolytic Enzymes, 3d ed. Oxford: Academic Press; 2012.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Jobs A., Abdin A., de Waha-Thiele S., et al. Angiotensin-converting-enzyme inhibitors in hemodynamic congestion: a meta-analysis of early studies. Clin. Res. Cardiol. 2019; 108 (11): 1240-8. doi: 10.1007/s00392-019-01456-4</mixed-citation><mixed-citation xml:lang="en">Jobs A., Abdin A., de Waha-Thiele S., et al. Angiotensin-converting-enzyme inhibitors in hemodynamic congestion: a meta-analysis of early studies. Clin. Res. Cardiol. 2019; 108 (11): 1240-8. doi: 10.1007/s00392-019-01456-4</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Dézsi C.A., Szentes V. Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on prothrombotic processes and myocardial infarction risk. Amer. J. Cardiovasc. Drugs. 2016; 16 (6): 399-406. doi: 10.1007/s40256-016-0185-0</mixed-citation><mixed-citation xml:lang="en">Dézsi C.A., Szentes V. Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on prothrombotic processes and myocardial infarction risk. Amer. J. Cardiovasc. Drugs. 2016; 16 (6): 399-406. doi: 10.1007/s40256-016-0185-0</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Holappa M., Vapaatalo H., Vaajanen A. Many faces of renin-angiotensin system - Focus on eye. The Open Ophthalmol. J. 2017; 11: 122-42. doi: 10.2174/1874364101711010122</mixed-citation><mixed-citation xml:lang="en">Holappa M., Vapaatalo H., Vaajanen A. Many faces of renin-angiotensin system - Focus on eye. The Open Ophthalmol. J. 2017; 11: 122-42. doi: 10.2174/1874364101711010122</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">White A.J.R., Cheruvu S.C., Sarris M. et al. Expression of classical components of the renin-angiotensin system in the human eye. J. Renin Angiotensin Aldosterone Syst. 2015; 16 (1): 59-66. doi: 10.1177/1470320314549791</mixed-citation><mixed-citation xml:lang="en">White A.J.R., Cheruvu S.C., Sarris M. et al. Expression of classical components of the renin-angiotensin system in the human eye. J. Renin Angiotensin Aldosterone Syst. 2015; 16 (1): 59-66. doi: 10.1177/1470320314549791</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Чеснокова Н.Б., Кост О.А., Никольская И.И. и др. Влияние местного применения ингибиторов ангиотензинпревращающего фермента на внутриглазное давление, гидродинамику глаза и активность ангиотензинпревращающего фермента в слезе и водянистой влаге (экспериментальное исследование). Российский офтальмологический журнал. 2009; 2 (1): 42-9.</mixed-citation><mixed-citation xml:lang="en">Chesnokova N.B., Kost O.A., Nikolskaya I.I., et al. The impact of topical application of angiotensin-converting enzyme inhibitors on intraocular pressure, eye hydrodynamics and the activity of angiotensin-converting enzyme in the tear and aqueous humor. An experimental study. Russian ophthalmological journal. 2009; 2 (1): 42-9 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Shah G.B., Sharma S., Mehta A.A., Goyal R.K. Oculohypotensive effect of angiotensinconverting enzyme inhibitors in acute and chronic models of glaucoma. J. Cardiovasc. Pharmacol. 2000; 36 (2): 169-75.</mixed-citation><mixed-citation xml:lang="en">Shah G.B., Sharma S., Mehta A.A., Goyal R.K. Oculohypotensive effect of angiotensinconverting enzyme inhibitors in acute and chronic models of glaucoma. J. Cardiovasc. Pharmacol. 2000; 36 (2): 169-75.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Чеснокова Н.Б., Кост О.А., Никольская И.И. и др. Экспериментальное обоснование местного применения ингибиторов ангиотензинпревращающего фермента для лечения ишемии тканей глаза на модели постожоговой ишемии конъюнктивы. Вестник офтальмологии. 2008; 124 (4): 28-31.</mixed-citation><mixed-citation xml:lang="en">Chesnokova N.B., Kost O.A., Nikol'skaia I.I., et al. Experimental rationale for local use of angiotensin-converting enzyme inhibitors for the treatment of ocular tissue ischemia on a model of postburn conjunctival ischemia. Vestnik Oftal'mologii. 2008; 124 (4): 28-31 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Чеснокова Н.Б., Григорьев А.В., Мустафаева К.Н. Способ моделирования ишемии глаза. Патент РФ № 2620014; 2017.</mixed-citation><mixed-citation xml:lang="en">Chesnokova N.B., Grigoryev A.V., Mustafayeva K.N. The way of eye ishemia modelling. Patent RF № 2620014; 2017 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Гулидова О.В., Любицкий О.Б., Клебанов Г.И., Чеснокова Н.Б. Изменение анти-окислительной активности слезной жидкости при экспериментальной ожоговой болезни глаз. Бюлл. экспер. биол. мед. 1999; 128 (11): 571-4. doi:10.1007/bf02433426</mixed-citation><mixed-citation xml:lang="en">Gulidova O.V., Lubitsky O.B., Klebanov G.I., Chesnokova N.B. Changes of tears antioxidant activity in experimental eye burns. Bulleten' Experimental'noy Biologii i Mediciny. 1999; 128 (11): 571-4 (in Russian). doi:10.1007/bf02433426</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Piquilloud T., Reinharz A., Roth M. Studies on the angiotensin converting enzyme with different substrates. Biochim. Biophys. Acta. 1970; 206 (1): 136-42.</mixed-citation><mixed-citation xml:lang="en">Piquilloud T., Reinharz A., Roth M. Studies on the angiotensin converting enzyme with different substrates. Biochim. Biophys. Acta. 1970; 206 (1): 136-42.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Ehlers M.R., Riordan J.F. Angiotensin-converting enzyme: new concepts concerning its biological role. Biochemistry. 1989; 28 (13): 5311-8.</mixed-citation><mixed-citation xml:lang="en">Ehlers M.R., Riordan J.F. Angiotensin-converting enzyme: new concepts concerning its biological role. Biochemistry. 1989; 28 (13): 5311-8.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Paul M., Poyan Mehr A., Kreutz R. Physiology of local renin-angiotensin systems. Physiol. Rev. 2006; 86 (3): 747-803. doi:10.1152/physrev.00036.2005</mixed-citation><mixed-citation xml:lang="en">Paul M., Poyan Mehr A., Kreutz R. Physiology of local renin-angiotensin systems. Physiol. Rev. 2006; 86 (3): 747-803. doi:10.1152/physrev.00036.2005</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Igic R. Four decades of ocular renin-angiotensin and kallikrein-kinin systems (1977-2017). Exp. Eye Res. 2018; 166: 74-83. doi: 10.1016/j.exer.2017.05.007</mixed-citation><mixed-citation xml:lang="en">Igic R. Four decades of ocular renin-angiotensin and kallikrein-kinin systems (1977-2017). Exp. Eye Res. 2018; 166: 74-83. doi: 10.1016/j.exer.2017.05.007</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Choudhary R., Singh M., Kapoor M.S., Singh A., Bodakhe S.H. Therapeutic targets of renin-angiotensin system in ocular disorders. J. Curr. Ophthalmol. 2016; 29 (1): 7-16. doi: 10.1016/j.joco.2016.09.009</mixed-citation><mixed-citation xml:lang="en">Choudhary R., Singh M., Kapoor M.S., Singh A., Bodakhe S.H. Therapeutic targets of renin-angiotensin system in ocular disorders. J. Curr. Ophthalmol. 2016; 29 (1): 7-16. doi: 10.1016/j.joco.2016.09.009</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Giese M.J., Speth R.C. The ocular renin-angiotensin system: a therapeutic target for the treatment of ocular disease. Pharmacol. Ther. 2014; 142 (1): 11-32. doi: 10.1016/j.pharmthera.2013.11.002</mixed-citation><mixed-citation xml:lang="en">Giese M.J., Speth R.C. The ocular renin-angiotensin system: a therapeutic target for the treatment of ocular disease. Pharmacol. Ther. 2014; 142 (1): 11-32. doi: 10.1016/j.pharmthera.2013.11.002</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Чеснокова Н.Б., Кост О.А., Никольская И.И. и др. Экспериментальное обоснование местного применения ингибиторов ангиотензинпревращающего фермента в лечении воспалительных процессов в глазу. Вестник офтальмологии. 2008; 124 (2): 16-9.</mixed-citation><mixed-citation xml:lang="en">Chesnokova N.B., Kost O.A., Nikol'skaia I.I., et al. Experimental rationale for local use of angiotensin-converting enzyme in the treatment of inflammatory processes in the eye. Vestnik Oftal'mologii. 2008; 124 (2): 16-19 (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Fukuda D., Enomoto S., Nagai R., Sata M. Inhibition of rennin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation. Biomed. Pharmacother. 2009; 63 (10): 754-61. doi: 10.1016/j.biopha.2009.02.006</mixed-citation><mixed-citation xml:lang="en">Fukuda D., Enomoto S., Nagai R., Sata M. Inhibition of rennin-angiotensin system attenuates periadventitial inflammation and reduces atherosclerotic lesion formation. Biomed. Pharmacother. 2009; 63 (10): 754-61. doi: 10.1016/j.biopha.2009.02.006</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
