Научная статья на тему 'MICRORNA AND VASCULAR PATHOLOGY OF THE EYE'

MICRORNA AND VASCULAR PATHOLOGY OF THE EYE Текст научной статьи по специальности «Клиническая медицина»

CC BY
60
27
i Надоели баннеры? Вы всегда можете отключить рекламу.
Ключевые слова
retinal vessel occlusion / microRNA / biomarkers / vascular pathology / retinal vessels / окклюзия сосудов сетчатки / микроРНК / биомаркеры / сосудистая патология / ретинальные сосуды

Аннотация научной статьи по клинической медицине, автор научной работы — Moshetova L.K., Usharova S.A., Turkina K.I., Sychev D.A., Saburina I.N.

Since the discovery of microRNAs just a few decades ago, our knowledge of these molecules and their potential as diagnostic biomarkers and therapeutic targets has significantly expanded. There is an ongoing discussion in the scientific community about the possibility of using microRNA for the diagnosis of cardiovascular diseases. It has been shown recently that levels of some microRNAs vary in vascular eye disorders, such as age-related macular degeneration and diabetic retinopathy. However, despite serious advances in our understanding of microRNA’s role in eye pathology, we still do not know whether it is possible to use microRNA as a biomarker for central retinal vein occlusion. Perhaps, the discovery of such candidate microRNAs will help in making the timely diagnosis and improve the quality of medical care in patients with retinal vein occlusion.

i Надоели баннеры? Вы всегда можете отключить рекламу.
iНе можете найти то, что вам нужно? Попробуйте сервис подбора литературы.
i Надоели баннеры? Вы всегда можете отключить рекламу.

МИКРОРНК И СОСУДИСТАЯ ПАТОЛОГИЯ ГЛАЗА

С момента открытия первой микроРНК несколько десятилетий назад представления о данных молекулах как о биомаркерах и потенциальных терапевтических мишенях различных заболеваний значительно расширились. В современном научном обществе активно обсуждают возможность применения микроРНК для диагностики сердечно-сосудистых заболеваний. Более того, ряд недавно проведенных исследований доказывает, что уровни определенных микроРНК варьируют и при сосудистых заболеваниях глаза, включающих возрастную макулярную дегенерацию и диабетическую ретинопатию. Однако, несмотря на прогресс в исследовании роли некоторых микроРНК в диагностике ряда офтальмологических патологий, информации о возможности использования микроРНК в качестве биомаркеров окклюзии центральной вены сетчатки на сегодняшний день нет. Возможно, что поиск и идентификация данных молекул смогут облегчить постановку диагноза и улучшить качество оказываемой медицинской помощи.

Текст научной работы на тему «MICRORNA AND VASCULAR PATHOLOGY OF THE EYE»

MicroRNA AND VASCULAR PATHOLOGY OF THE EYE

Moshetova LK, Usharova SA Turkina KI, Sychev DA, Saburina IN

Russian Medical Academy of Continuous Professional Education, Moscow, Russia

Since the discovery of microRNAs just a few decades ago, our knowledge of these molecules and their potential as diagnostic biomarkers and therapeutic targets has significantly expanded. There is an ongoing discussion in the scientific community about the possibility of using microRNA for the diagnosis of cardiovascular diseases. It has been shown recently that levels of some microRNAs vary in vascular eye disorders, such as age-related macular degeneration and diabetic retinopathy. However, despite serious advances in our understanding of microRNA's role in eye pathology, we still do not know whether it is possible to use microRNA as a biomarker for central retinal vein occlusion. Perhaps, the discovery of such candidate microRNAs will help in making the timely diagnosis and improve the quality of medical care in patients with retinal vein occlusion.

Keywords: retinal vessel occlusion, microRNA, biomarkers, vascular pathology, retinal vessels

Author contribution: Moshetova LK — concept and manuscript preparation; Usharova SA, Turkina KI — literature analysis and manuscript preparation; Sychev DA, Saburina IN — manuscript preparation.

^<1 Correspondence should be addressed: Svetlana A. Usharova Barrikadnaya, 2/1, str. 1, Moscow, 125993, svetlalextar@gmail.com

Received: 26.06.2020 Accepted: 09.07.2020 Published online: 15.07.2020

DOI: 10.24075/brsmu.2020.042

МикроРНК И СОСУДИСТАЯ ПАТОЛОГИЯ ГЛАЗА

Л. К. Мошетова, С. А. Ушарова К. И. Туркина, Д. А. Сычев, И. Н. Сабурина Российская медицинская академия непрерывного профессионального образования, Москва, Россия

С момента открытия первой микроРНК несколько десятилетий назад представления о данных молекулах как о биомаркерах и потенциальных терапевтических мишенях различных заболеваний значительно расширились. В современном научном обществе активно обсуждают возможность применения микроРНК для диагностики сердечно-сосудистых заболеваний. Более того, ряд недавно проведенных исследований доказывает, что уровни определенных микроРНК варьируют и при сосудистых заболеваниях глаза, включающих возрастную макулярную дегенерацию и диабетическую ретинопатию. Однако, несмотря на прогресс в исследовании роли некоторых микроРНК в диагностике ряда офтальмологических патологий, информации о возможности использования микроРНК в качестве биомаркеров окклюзии центральной вены сетчатки на сегодняшний день нет. Возможно, что поиск и идентификация данных молекул смогут облегчить постановку диагноза и улучшить качество оказываемой медицинской помощи. Ключевые слова: окклюзия сосудов сетчатки, микроРНК, биомаркеры, сосудистая патология, ретинальные сосуды

Вклад авторов: Л. К. Мошетова — определение концепции рукописи и ее редактирование; С. А. Ушарова, К. И. Туркина — подбор и анализ литературы, подготовка рукописи; Д. А. Сычев, И. Н. Сабурина — редактирование рукописи.

[><3 Для корреспонденции: Светлана Александровна Ушарова

ул. Баррикадная, д. 2/1, стр. 1, г. Москва, 125993; svetlalextar@gmail.com

Статья получена: 26.06.2020 Статья принята к печати: 09.07.2020 Опубликована онлайн: 15.07.2020 DOI: 10.24075/vrgmu.2020.042

Making a timely and accurate diagnosis is crucial for effective treatment and positive clinical outcomes. This cannot be any truer for vascular disorders. MicroRNAs (miRNAs) were discovered back in 1993 [1]. They are a class of single-stranded non-coding RNAs constituted by 16 to 27 (an average of 22) nucleotides [2]. Transcription of miRNA precursor genes is regulated by genomic DNA methylation and histone modifications, which, in turn, vary across pathologies [3]. All around the globe, research teams are actively exploring the possibility of using miRNA as a diagnostic biomarker for a broad range of health conditions. Although it is not yet common practice to use miRNAs as biomarkers of eye diseases, such as retinal vessel occlusion, the ongoing research into their role in systemic vascular pathology suggests that they are potent diagnostic tools.

MicroRNA and systemic vascular pathology

There is a huge body of evidence that miRNA expression is changed significantly in systemic and localized vascular pathologies; the amassed data suggest tremendous diagnostic potential for miRNA and, specifically, circulating miRNA [4]. Circulating miRNA levels reflect physiological and pathological changes in the body, including cardiovascular and

neurodegenerative disorders. For example, miR-1, miR-133b, miR-145, miR-208b, miR-499, miR-133a, and miR-208a are diagnostic biomarkers for coronary artery disease [5].

Patients with atherosclerosis have significantly elevated miR-122, miR-21, miR-130a, miR-211c and low miR92a, miR-222, miR-126 in their blood [6]. In addition to their diagnostic potential, these miRNAs and their inhibitors can be used to treat atherosclerosis [7].

Ischemic stroke and myocardial infarction are the most severe complications of atherosclerosis. Multiple studies conducted on animal models and human patients indicate a link between the levels of circulating and tissue microRNAs and ischemic stroke or its effects. In the acute phase of ischemic stroke, miR-124 and miR-21 are elevated whereas miR-221 concentrations decline; elevated miR-145 and miR-210 are predictors of a more favorable outcome [8]. Changes in miRNA levels are also reported in patients with myocardial infarction; specifically, such patients demonstrate a sharp decrease in miR-375 expression [9].

Hypertension is the most prevalent cardiovascular condition. It is a risk factor for many vascular disorders, including eye disorders. A Russian study investigated the profiles of miR-126, miR-155, miR-221, and miR-222 in hypertensive patients and healthy volunteers. Increased dispersion was observed for all

studied miRNA in all hypertensive patients, as compared with healthy individuals. MiR-221 prevailed in hypertensive patients, whereas miR-126, in healthy volunteers [10].

Thus, the levels of some circulating miRNAs change in patients with systemic vascular disorders and therefore might be a potent candidate diagnostic biomarkers. Because systemic vascular disorders and vascular eye disorders have the same pathogenesis, there might be microRNAs that could act as biomarkers for conditions associated with impeded retinal blood flow. So far, no qualitative and quantitative miRNA analysis has been conducted for retinal vessel occlusion but the available data on changes in microRNA profiles accompanying vascular eye disorders suggest this research field holds great promise.

MicroRNA in age-related macular degeneration

Age-related macular degeneration (AMD) is the primary cause of irreversible central vision loss in elderly people. Choroidal neovascularization (CNV) leads to increased vascular permeability, fluid exudation, and irreversible damage to photoreceptor cells, causing vision decline. Being a complex progressive disease, AMD is linked to genetic (including complementary) and environmental factors [11]. Some miRNAs associated with complementary factors were found to change their regulation function in the blood and ocular tissue of patients with AMD. A PCR-based study of 384 miRNAs in the blood plasma of patients with AMD revealed that characteristics of 16 miRNAs were significantly changed in such patients and 10 other microRNAs were expressed only in individuals with exudative AMD [12]. A team of Italian researchers studied the expression profiles of different microRNAs in patients with or without AMD and in rats with experimentally induced retinal pathology. The levels of miR-9, miR-23a, miR-27a, miR-34a, miR-146a, and miR-155 were significantly different between diseased and healthy individuals. The most pronounced differences were observed for miR-27a, miR-146a and miR-155, suggesting they might have potential as biomarkers and therapeutic targets for treating AMD [13].

MicroRNA in diabetic retinopathy

The possibility of using microRNAs as biomarkers is being considered for diabetic retinopathy (DR), another serious visual impairment arising from a vascular disorder. DR is a common microvascular complication of diabetes mellitus (DM), which is currently recognized as a global epidemic. DR results from damage to microvessels following prolonged exposure to hyperglycemia. Progressive retinal ischemia triggers expression

Table 1. Expression of candidate microRNAs in different pathologies

of hypoxia-inducible growth factors, including VEGF, which, in turn, stimulate retinal neovascularization [14]. Consequently, the blood-retinal barrier breaks down, leading to vascular leakage and retinal edema [15]. The analysis of circulating miRNAs isolated from serum and plasma samples of patients with and without DR revealed changes in the expression of many miRNAs in patients of different age, with different DM types, different time of onset, etc. [16]. There were reports of quantitative and qualitative changes in the profiles of miR-126 [17-19], miR-150 [20], miR-155 [21], and miR-200b isolated from patients with DR. Of all those miRNAs, miR-155 and miR-126 had the highest clinical relevance [22]. A research group from China compared serum levels of miR-126 in patients with DR and healthy volunteers by means of real-time PCR and found statistically significant differences in miR-126 expression between the two cohorts. According to the analysis of blood serum samples collected from patients with proliferative (PDT) and non-proliferative (NPDT) diabetic retinopathies, miR-126 levels varied across patients with retinal pathology depending on its severity. MiR-126 concentrations were declining as proliferative retinal pathology was progressing. The researchers were able to determine the diagnostic thresholds for miR-126 that could be used to predict the risk of PDT and NPDT and detect borderline conditions at high risk of transformation into PDT. The researchers pointed out that miR-126 could be used as a biomarker of retinal endothelial damage and early stages of PDT [17].

Using this information, we shortlisted a few microRNA candidates that in our opinion have the best diagnostic and prognostic potential as candidate biomarkers of retinal vein occlusion (Table).

miR-126

MiR-126 is one of the key pro-angiogenic microRNAs that regulate expression of some growth factors, including VEGF and FGF [23, 24]. MicroRNA expression profiles were studied on several animal models of human vascular eye disorders, including oxygen-induced retinopathy (DR-type neovascularization) and laser-induced CNV (wet ARMD). MiR-126 concentrations declined in the choroid of mice with laser-induced CNV [25] and also in the retina and choroid of rodents with oxygen-induced retinopathy [26]. Besides, mice with decreased miR-126 concentrations had signs of damage to the peripheral choroid [27]; stimulated elevation of miR-126 was shown to inhibit retinal neovascularization and breakdown of the blood-retinal barrier in mice with oxygen-induced retinopathy [28]. These findings suggest that miR-126 might be an important biomarker mirroring the condition of

miR-126 miR-155 miR-21

Vascular disorders

Atherosclerosis microRNA expression decreases [6] [6]* microRNA expression increases [6]

Ischemic stroke microRNA expression decreases [36] [36]* microRNA expression increases [36]

Hypertension microRNA expression increases [10] [10]* microRNA expression increases [38]

Coronary artery disease microRNA expression increases [10, 24] [10, 39]* microRNA expression increases [38]

Eye disorders

Diabetic retinopathy microRNA expression decreases [17-19, 22] microRNA expression increases [31] microRNA expression increases [40]

Age-related macular degeneration microRNA expression decreases [23-25] microRNA expression increases [13] microRNA expression increases [35]

Note: *— Changes in microRNA expression depend on the character of the pathology.

the choroid in various pathologies and a potential therapeutic target for developing new approaches to the management of eye disorders.

miR-155

MiR-155 is a proinflammatory microRNA that is specifically expressed in atherosclerotic plaques and proinflammatory M1 macrophages [6]. Retinal miR-155 expression undergoes significant changes in wet ARMD, experimental oxygen-induced retinopathy [29], light-induced retinal degeneration [30], and streptozotocin-induced DR [31]. Its deficit leads to the shrinkage of vascular areas and neovascularization in the rodent model of oxygen-induced retinopathy [29]. Besides, miR-155 was proved to regulate the levels of complement factor H in ARMD [32], maintaining its role in the angiogenesis and inflammation in a range of eye disorders. MiR-155 is an important biomarker that reflects the unfolding of the proinflammatory cascades accompanying the progression of vascular disorders. In addition, this miRNA is being investigated as a potential therapeutic target in eye pathology.

miR-21

MiR-21 is known to be linked to tumor formation and neovascularization [33]. Its expression changes in cardiac pathology [34]. MiR-21 plays a crucial role in the pathogenesis

of ARMD. It participates in the regulation of retinal vessel growth, which can be inferred from high miR-21 expression in retinal endothelial cells. Increased miR-21 expression was detected in the experimental mouse model of laser-induced CNV. In another study, stimulation of miR-21 expression inhibited proliferation and migration of cultured endothelial cells through targeted inhibition of certain proteins that affect the dynamics of actin networks [35]. This indicates the diagnostic and modulating potential of miR-21.

CONCLUSIONS

There is a paucity of research studies looking at the expression profiles of miRNA genes in eye pathology. Nevertheless, the available data suggests that miRNAs might hold great promise as potent diagnostic markers of eye disorders, such as retinal vein occlusion. The comprehensive analysis of their expression will help to conduct minimally invasive screening, provide adequate treatment and take timely prevention measures. It is important to develop microRNA panels and determine their threshold values that signal the risk of complications in patients during or after therapy.

Further basic and clinical research on complex 3D organoid and spheroid models is needed to better understand the role of individual microRNAs or their clusters and to evaluate their diagnostic and therapeutic potential in retinal vascular pathology.

References

1. Lee RC, Feinbaum RL, Ambros V The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993; 75 (5): 843-54. DOI: 10.1016/0092-8674(93)90529-y.

2. Fang Z, Du R, Edwards A, Flemington EK, Zhang K. The Sequence Structures of Human MicroRNA Molecules and Their Implications. PLoS ONE. 2013; 8 (1): e54215. Available from: https://doi.org/10.1371/journal.pone.0054215.

3. Kucher AN, Babushkina NP. Role of microRNA, genes involved in their biogenesis and functioning in the development of human disorders. Medical Genetics. 2011; 1: 3-13. Russian.

4. Pogribny IP. MicroRNAs as biomarkers for clinical studies. Exp Biol Med (Maywood). 2018; 243 (3): 283-90. DOI: 10.1177/1535370217731291.

5. Navickas R, Gal D, Laucevicius A, Taparauskaitè A, Zdanytè M, Holvoet P. Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review. Cardiovasc Res. 2016; 111 (4): 322-37. DOI: 10.1093/cvr/cvw174.

6. Kucher AN, Nazarenko MS. The role of microRNA in atherogenesis. Kardiologija. 2017; 57 (9): 65-76. Available from: https://doi. org/10.18087/cardio.2017.9.10022. Russian.

7. Koroleva IA, Nazarenko MS, Kucher AN. Role of microRNA in development of instability of atherosclerotic plaque. Biochemistry. 2018; 83 (1): 34-46. Russian.

8. Gareev IF, Beilerly OA. Role of microRNA in ischemic stroke. Neurologic magazine. 2018; 23 (4): 166-75. Russian.

9. Baulina N, Osmak G, Kiselev I, et al. NGS-identified circulating miR-375 as a potential regulating component of myocardial infarction associated network. J Mol Cell Cardiol. 2018; 121: 173-9. DOI: 10.1016/j.yjmcc.2018.07.129.

10. Shheglova NE, Kalinkin MN. Kachestvennye harakteristiki miR-126, miR-155, miR-221, miR-222 u bol'nyh gipertonicheskoj bolezn'ju i postinfarktnym kardiosklerozom [dissertacija]. K., 2015. Russian.

11. Coleman HR, Chan CC, Ferris FL 3rd, Chew EY. Age-related macular degeneration. Lancet. 2008; 372 (9652): 1835-45. DOI: 10.1016/S0140-6736(08)61759-6.

12. Ertekin S, Yildirim O, Dinç E, et al. Evaluation of circulating miRNAs

in wet age-related macular degeneration. Molecular Vision. 2014; 20: 1057-66.

13. Romano GL, Platania CBM, Drago F, et al. Retinal and circulating miRNAs in age-related macular degeneration: an in vivo animal and human study. Front Pharmacol. 2017; 8: 168. DOI: 10.3389/ fphar.2017.00168.

14. Fong DS, Aiello LP, Ferris FL, Klein R. Diabetic retinopathy. Diabetes Care. 2004 Oct; 27 (10): 2540-53. Available from: https://doi.org/10.2337/diacare.27.10.2540.

15. Qazi Y, Maddula S, Ambati BK. Mediators of ocular angiogenesis. J Genet. 2009; 88 (4): 495-515. DOI: 10.1007/s12041-009-0068-0.

16. Qing S, Yuan S, Yun C, et al. Serum miRNA biomarkers serve as a fingerprint for proliferative diabetic retinopathy. Cell Physiol Biochem. 2014; 34 (5): 1733-40. DOI: 10.1159/000366374.

17. Qin LL, An MX, Liu YL, Xu HC, Lu ZQ. MicroRNA-126: a promising novel biomarker in peripheral blood for diabetic retinopathy. Int J Ophthalmol. 2017; 10 (4): 530-4. DOI: 10.18240/ijo.2017.04.05.

18. Barutta F, Bruno G, Matullo G, et al. MicroRNA-126 and micro-/ macrovascular complications of type 1 diabetes in the EURODIAB Prospective Complications Study. Acta Diabetol. 2017; 54 (2): 133-9. DOI: 10.1007/s00592-016-0915-4.

19. Rezk NA, Sabbah NA, Saad MS. Role of MicroRNA 126 in screening, diagnosis, and prognosis of diabetic patients in Egypt. IUBMB Life. 2016; 68 (6): 452-8. DOI: 10.1002/iub.1502.

20. Mazzeo A, Beltramo E, Lopatina T, Gai C, Trento M, Porta M. Molecular and functional characterization of circulating extracellular vesicles from diabetic patients with and without retinopathy and healthy subjects. Exp Eye Res. 2018; 176: 6977. DOI: 10.1016/j.exer.2018.07.003.

21. Yang TT, Song SJ, Xue HB, Shi DF, Liu CM, Liu H. Regulatory T cells in the pathogenesis of type 2 diabetes mellitus retinopathy by miR-155. Eur Rev Med Pharmacol Sci. 2015; 19 (11): 2010-5.

22. Li EH, Huang QZ, Li GC, Xiang ZY, Zhang X. Effects of miRNA-200b on the development of diabetic retinopathy by targeting VEGFA gene. Biosci Rep. 2017; 37 (2): BSR20160572. DOI: 10.1042/BSR20160572.

23. Wang S, Aurora AB, Johnson BA, et al. The endothelial-

specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008; 15 (2): 261-71. DOI: 10.1016/j. devcel.2008.07.002.

24. Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008; 15 (2): 272-84. DOI: 10.1016/j.devcel.2008.07.008.

25. Wang L, Lee AY, Wigg JP, Peshavariya H, Liu P, Zhang H. miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model. Int J Mol Sci. 2016; 17 (6): 895. DOI: 10.3390/ijms17060895.

26. Desjarlais M, Rivera JC, Lahaie I, Cagnone G, Wirt M, Omri S, et al. MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model. PLoS ONE. 2019; 14 (6): e0218282. Available from: https://doi.org/10.1371/journal.pone.0218282

27. Zhao F, Anderson C, Karnes S, et al. Expression, regulation and function of miR-126 in the mouse choroid vasculature. Exp Eye Res. 2018; 170: 169-76. DOI: 10.1016/j.exer.2018.02.026

28. Bai X, Luo J, Zhang X, et al. MicroRNA-126 Reduces Blood-Retina Barrier Breakdown via the Regulation of VCAM-1 and BCL2L11 in Ischemic Retinopathy. Ophthalmic Research. 2017; 57 (3): 173-85. DOI: 10.1159/000454716.

29. Yan L, Lee S, Lazzaro DR, Aranda J, Grant MB, Chaqour B. Single and Compound Knock-outs of MicroRNA (miRNA)-155 and Its Angiogenic Gene Target CCN1 in Mice Alter Vascular and Neovascular Growth in the Retina via Resident Microglia. J Biol Chem. 2015; 290 (38): 23264-81. DOI: 10.1074/jbc. M115.646950.

30. Pilakka-Kanthikeel S, Raymond A, Atluri VS, et al. Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes is regulated by miRNA-181a. J Neuroinflammation. 2015; 12: 66. DOI: 10.1186/ s12974-015-0285-9.

31. Kovacs B, Lumayag S, Cowan C, Xu S. MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Invest

Литература

1. Lee RC, Feinbaum RL, Ambros V The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993; 75 (5): 843-54. DOI: 10.1016/0092-8674(93)90529-y.

2. Fang Z, Du R, Edwards A, Flemington EK, Zhang K. The Sequence Structures of Human MicroRNA Molecules and Their Implications. PLoS ONE. 2013; 8 (1): e54215. Available from: https://doi.org/10.1371/journal.pone.0054215.

3. Кучер А. Н., Бабушкина Н. П. Роль микро-РНК, генов, их биогенеза и функционирования в развитии патологических состояний у человека. Медицинская генетика. 2011; 1: 3-13.

4. Pogribny IP. MicroRNAs as biomarkers for clinical studies. Exp Biol Med (Maywood). 2018; 243 (3): 283-90. DOI: 10.1177/1535370217731291.

5. Navickas R, Gal D, Laucevicius A, Taparauskaite A, Zdanyte M, Holvoet P. Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review. Cardiovasc Res. 2016; 111 (4): 322-37. DOI: 10.1093/cvr/cvw174.

6. Кучер А. Н., Назаренко М. С. Роль микро-РНК при атерогенезе. Кардиология. 2017; 57 (9): 65-76. Available from: https://doi.org/10.18087/cardio.2017.9.10022.

7. Королева Ю. А., Назаренко М. С., Кучер А. Н. Роль микроРНК в формировании нестабильных атеросклеротических бляшек. Биохимия. 2018; 83 (1): 34-46.

8. Гареев И. Ф., Бейлерли О. А. Роль микро-РНК в ишемическом инсульте. Неврологический журнал. 2018; 23 (4), 166-75.

9. Baulina N, Osmak G, Kiselev I, et al. NGS-identified circulating miR-375 as a potential regulating component of myocardial infarction associated network. J Mol Cell Cardiol. 2018; 121: 173-9. DOI: 10.1016/j.yjmcc.2018.07.129.

10. Щеглова Н. Е., Калинкин М. Н. Качественные характеристики miR-126, miR-155, miR-221, miR-222 у больных гипертонической болезнью и постинфарктным кардиосклерозом [диссертация]. К., 2015.

11. Coleman HR, Chan CC, Ferris FL 3rd, Chew EY. Age-related

Ophthalmol Vis Sci. 2011; 52 (7): 4402-9. DOI: 10.1167/iovs.10-6879.

32. Lukiw WJ, Surjyadipta B, Dua P, Alexandrov PN. Common micro RNAs (miRNAs) target complement factor H (CFH) regulation in Alzheimer's disease (AD) and in age-related macular degeneration (AMD). Int J Biochem Mol Biol. 2012; 3 (1): 105-16.

iНе можете найти то, что вам нужно? Попробуйте сервис подбора литературы.

33. Liu HY, Zhang YY, Zhu BL, et al. miR-21 regulates the proliferation and apoptosis of ovarian cancer cells through PTEN/PI3K/AKT. Eur Rev Med Pharmacol Sci. 2019; 23 (10): 4149-55. DOI: 10.26355/eurrev_201905_17917.

34. Yuan J, Chen H, Ge D, et al. Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7. Cell Physiol Biochem. 2017; 42 (6): 2207-19. DOI: 10.1159/000479995.

35. Sabatel C, Malvaux L, Bovy N, et al. MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells. PLoS One. 2011; 6 (2): e16979. DOI: 10.1371/ journal.pone.0016979.

36. Aitbaev KA, Murkamilov IT, Fomin VV, Murkamilova JA, Yusupov FA. MicroRNA in ischemic stroke. Journal of Neurology and Psychiatry named after S.S. Korsakov. Special Issues. 2018; 118 (3): 48-56. Available from: https://doi.org/10.17116/jnevro20181183248-56. Russian.

37. Li X, Wei Y, Wang Z. microRNA-21 and hypertension. Hypertens Res. 2018; 41: 649-61. Available from: https://doi.org/10.1038/ s41440-018-0071-z.

38. Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456 (7224): 980-4. DOI: 10.1038/ nature07511.

39. Fichtlscherer S, De Rosa S, Fox H, et al. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010; 107 (5): 677-84. DOI: 10.1161/CIRCRESAHA.109.215566.

40. Chen Q, Qiu F, Zhou K, et al. Pathogenic Role of microRNA-21 in Diabetic Retinopathy Through Downregulation of PPARa. Diabetes. 2017; 66 (6): 1671-82. DOI: 10.2337/db16-1246.

macular degeneration. Lancet. 2008; 372 (9652): 1835-45. DOI: 10.1016/S0140-6736(08)61759-6.

12. Ertekin S, Yildirim O, Din? E, et al. Evaluation of circulating miRNAs in wet age-related macular degeneration. Molecular Vision. 2014; 20: 1057-66.

13. Romano GL, Platania CBM, Drago F, et al. Retinal and circulating miRNAs in age-related macular degeneration: an in vivo animal and human study. Front Pharmacol. 2017; 8: 168. DOI: 10.3389/ fphar.2017.00168.

14. Fong DS, Aiello LP, Ferris FL, Klein R. Diabetic retinopathy. Diabetes Care. 2004 Oct; 27 (10): 2540-53. Available from: https://doi.org/10.2337/diacare.27.10.2540.

15. Qazi Y, Maddula S, Ambati BK. Mediators of ocular angiogenesis. J Genet. 2009; 88 (4): 495-515. DOI: 10.1007/s12041-009-0068-0.

16. Qing S, Yuan S, Yun C, et al. Serum miRNA biomarkers serve as a fingerprint for proliferative diabetic retinopathy. Cell Physiol Biochem. 2014; 34 (5): 1733-40. DOI: 10.1159/000366374.

17. Qin LL, An MX, Liu YL, Xu HC, Lu ZQ. MicroRNA-126: a promising novel biomarker in peripheral blood for diabetic retinopathy. Int J Ophthalmol. 2017; 10 (4): 530-4. DOI: 10.18240/ijo.2017.04.05.

18. Barutta F, Bruno G, Matullo G, et al. MicroRNA-126 and micro-/ macrovascular complications of type 1 diabetes in the EURODIAB Prospective Complications Study. Acta Diabetol. 2017; 54 (2): 133-9. DOI: 10.1007/s00592-016-0915-4.

19. Rezk NA, Sabbah NA, Saad MS. Role of MicroRNA 126 in screening, diagnosis, and prognosis of diabetic patients in Egypt. IUBMB Life. 2016; 68 (6): 452-8. DOI: 10.1002/iub.1502.

20. Mazzeo A, Beltramo E, Lopatina T, Gai C, Trento M, Porta M. Molecular and functional characterization of circulating extracellular vesicles from diabetic patients with and without retinopathy and healthy subjects. Exp Eye Res. 2018; 176: 6977. DOI: 10.1016/j.exer.2018.07.003.

21. Yang TT, Song SJ, Xue HB, Shi DF, Liu CM, Liu H. Regulatory T cells in the pathogenesis of type 2 diabetes mellitus retinopathy

by miR-155. Eur Rev Med Pharmacol Sci. 2015; 19 (11): 2010-5.

22. Li EH, Huang QZ, Li GC, Xiang ZY, Zhang X. Effects of miRNA-200b on the development of diabetic retinopathy by targeting VEGFA gene. Biosci Rep. 2017; 37 (2): BSR20160572. DOI: 10.1042/BSR20160572.

23. Wang S, Aurora AB, Johnson BA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008; 15 (2): 261-71. DOI: 10.1016/j. devcel.2008.07.002.

24. Fish JE, Santoro MM, Morton SU, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008; 15 (2): 272-84. DOI: 10.1016/j.devcel.2008.07.008.

25. Wang L, Lee AY, Wigg JP, Peshavariya H, Liu P, Zhang H. miR-126 Regulation of Angiogenesis in Age-Related Macular Degeneration in CNV Mouse Model. Int J Mol Sci. 2016; 17 (6): 895. DOI: 10.3390/ijms17060895.

26. Desjarlais M, Rivera JC, Lahaie I, Cagnone G, Wirt M, Omri S, et al. MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model. PLoS ONE. 2019; 14 (6): e0218282. Available from: https://doi.org/10.1371/journal.pone.0218282

27. Zhao F, Anderson C, Karnes S, et al. Expression, regulation and function of miR-126 in the mouse choroid vasculature. Exp Eye Res. 2018; 170: 169-76. DOI: 10.1016/j.exer.2018.02.026

28. Bai X, Luo J, Zhang X, et al. MicroRNA-126 Reduces Blood-Retina Barrier Breakdown via the Regulation of VCAM-1 and BCL2L11 in Ischemic Retinopathy. Ophthalmic Research. 2017; 57 (3): 173-85. DOI: 10.1159/000454716.

29. Yan L, Lee S, Lazzaro DR, Aranda J, Grant MB, Chaqour B. Single and Compound Knock-outs of MicroRNA (miRNA)-155 and Its Angiogenic Gene Target CCN1 in Mice Alter Vascular and Neovascular Growth in the Retina via Resident Microglia. J Biol Chem. 2015; 290 (38): 23264-81. DOI: 10.1074/jbc. M115.646950.

30. Pilakka-Kanthikeel S, Raymond A, Atluri VS, et al. Sterile alpha motif and histidine/aspartic acid domain-containing protein 1 (SAMHD1)-facilitated HIV restriction in astrocytes is regulated by miRNA-181a. J Neuroinflammation. 2015; 12: 66. DOI: 10.1186/

s12974-015-0285-9.

31. Kovacs B, Lumayag S, Cowan C, Xu S. MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci. 2011; 52 (7): 4402-9. DOI: 10.1167/iovs.10-6879.

32. Lukiw WJ, Surjyadipta B, Dua P, Alexandrov PN. Common micro RNAs (miRNAs) target complement factor H (CFH) regulation in Alzheimer's disease (AD) and in age-related macular degeneration (AMD). Int J Biochem Mol Biol. 2012; 3 (1): 105-16.

33. Liu HY, Zhang YY, Zhu BL, et al. miR-21 regulates the proliferation and apoptosis of ovarian cancer cells through PTEN/PI3K/AKT. Eur Rev Med Pharmacol Sci. 2019; 23 (10): 4149-55. DOI: 10.26355/eurrev_201905_17917.

34. Yuan J, Chen H, Ge D, et al. Mir-21 Promotes Cardiac Fibrosis After Myocardial Infarction Via Targeting Smad7. Cell Physiol Biochem. 2017; 42 (6): 2207-19. DOI: 10.1159/000479995.

35. Sabatel C, Malvaux L, Bovy N, et al. MicroRNA-21 exhibits antiangiogenic function by targeting RhoB expression in endothelial cells. PLoS One. 2011; 6 (2): e16979. DOI: 10.1371/ journal.pone.0016979.

36. Айтбаев К. А., Муркамилов И. Т., Фомин В. В., Муркамилова Ж. А., Юсупов Ф. А. МикроРНК при ишемическом инсульте. Журнал неврологии и психиатрии им. С. С. Корсакова. Спецвыпуски. 2018; 118 (3): 48-56. Available from: https://doi.org/10.17116/ jnevro20181183248-56.

37. Li X, Wei Y, Wang Z. microRNA-21 and hypertension. Hypertens Res. 2018; 41: 649-61. Available from: https://doi.org/10.1038/ s41440-018-0071-z.

38. Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008; 456 (7224): 980-4. DOI: 10.1038/ nature07511.

39. Fichtlscherer S, De Rosa S, Fox H, et al. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010; 107 (5): 677-84. DOI: 10.1161/CIRCRESAHA.109.215566.

40. Chen Q, Qiu F, Zhou K, et al. Pathogenic Role of microRNA-21 in Diabetic Retinopathy Through Downregulation of PPARa. Diabetes. 2017; 66 (6): 1671-82. DOI: 10.2337/db16-1246.

i Надоели баннеры? Вы всегда можете отключить рекламу.