THE ROLE OF TREATMENT OF THROMBOCYTE REACTIVITY IN THE PROGRESS OF DIABETIC MAKULOPATHY AND THE INITIALIZATION OF THE DIABETIC MACULAR EDEMA IN DIABETES MELLITUS 2 TYPE
About the author:
Mogilevskyy S. Yu., Panchenko Yu. A., Ziablittsev S. V.
Heading:
CLINICAL AND EXPERIMENTAL MEDICINE
Type of article:
Scentific article
Annotation:
The aim of the study was to elucidate the reactivity of platelets (PL) in the progression of diabetic maculopathy (DMP) with moderate and severe stages of non-proliferative diabetic retinopathy (NDPR) and development of diabetic macular edema (DME). Object and methods of investigation. The study included 29 patients (29 eyes) with diabetes mellitus (DM) of type 2 who, according to the results of the clinical and instrumental examination and according to the ETDRS classification, detected DMP with moderate (18 patients, 18 eyes) and severe (11 patients, 11 eyes) NPDR. For the study of PL in vitro, agonists involved in the pathogenesis of DM 2 type: adenosine diphosphate (ADP), epinephrine, angiotensin-2 (Ang-2), platelet activating factor (PAF), and collagen were used in vitro. The PL aggregation was evaluated by the turbidimetric method using the ChronoLog analyzer (USA). Results of the study. In patients with DMP with moderate and severe stages of NPDR, PL hyperreactivity was observed with respect to collagen, epinephrine, Ang-2 and PAF. The risk factor for the progression of DMP was an increase in the activity of the purineergic retinal system, which was manifested by an increase in the reactivity of adenosine receptors to ADP. The severity of the activation of the renin-angiotensin system and the inflammatory response, which was manifested by the hyperreactivity of PL in response to Ang-2 and PAF, was the reason for the development of DME. Conclusions. In the progression of DMP, activation of sympathetic-adrenal and renin-angiotensin systems, inflammation and remodeling of the intercellular matrix of retinal connective tissue, manifested itself in the growth of PL functional activity, capable of reproducing thrombosis and inflammation in the retina of the eye. Hyperreactivity of PL in response to Ang-2 and PAF was the reason for the development of DME, and, consequently, the sensitivity of AT1- and PAF-receptors of PL can be used to predict the development of DME.
Tags:
diabetic maculopathy, diabetic macular edema, non-proliferative diabetic retinopathy, platelet aggregation
Bibliography:
- Daruich A, Matet A, Moulin A, Kowalczuk L, Nicolas M, Sellam A, et al. Mechanisms of macular edema: Beyond the surface. Prog Retin Eye Res. 2018;63:20-68.
- Xu J, Chen LJ, Yu J, Wang HJ, Zhang F, Liu Q, et alhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Wu%20J%5BAuthor%5D&cauthor=true&c author_uid=30025404. Involvement of advanced glycation end products in the pathogenesis of diabetic retinopathy. Cell Physiol Biochem. 2018;48(2):705-17.
- Urias EA, Urias GA, Monickaraj F, McGuire P, Das A. Novel therapeutic targets in diabetic macular edema: Beyond VEGF. Vision Res. 2017;139:221-7.
- Sorrentino FS, Matteini S, Bonifazzi C, Sebastiani A, Parmeggiani F. Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction. Eye (Lond). 2018;32(7):1157-63.
- Jiang Y, Zhang Q, Steinle JJ. Beta-adrenergic receptor agonist decreases VEGF levels through altered eNOS and PKC signaling in diabetic retina. Growth Factors. 2015;33(3):192-9.
- Kim JH, Kim JH, Yu YS, Cho CS, Kim KW. Blockade of angiotensin II attenuates VEGF-mediated blood-retinal barrier breakdown in diabetic retinopathy. J Cereb Blood Flow Metab. 2009;29(3):621-8.
- Dagher Z, Gerhardinger C, Vaz J, Goodridge M, Tecilazich F, Lorenzi M. The increased transforming growth factor-β signaling induced by diabetes protects retinal vessels. Am J Pathol. 2017;187(3):627-38.
- Imai S, Otsuka T, Naito A, Shimazawa M, Hara H. Triamcinolone acetonide suppresses inflammation and facilitates vascular barrier function in human retinal microvascular endothelial cells. Curr Neurovasc Res. 2017;14(3):232-41.
- Deppermann C, Kubes P. Start a fire, kill the bug: the role of platelets in inflammation and infection. Innate Immun. 2018 Jul;26:1753425918789255.
- Ed Rainger G, Chimen M, Harrison MJ, Yates CM, Harrison P, Watson SP, et al. The role of platelets in the recruitment of leukocytes during vascular disease. Platelets. 2015;26(6):507-20.
- Kazimierczyk R, Kamiński K. The role of platelets in the development and progression of pulmonary arterial hypertension. Adv Med Sci. 2018;63(2):312-6.
- Greco NJ, Arnold JH, O’Dorisio TM, Cataland S, Panganamala RV. Action of platelet-activating factor on type 1 diabetic human platelets. J Lab Clin Med. 1985;105(4):410-6.
- Barinov EF, Sulayeva ON, Gnilorybov AM. Trombotsity. Donetsk: «Novyy Mir», 2012. 316 s. [in Russiаn].
- Hudz AS, Mogilevskyy SIu, Maksymtsiv ML. Functional status of platelets in type 2 diabetes patients showing no diabetic fundus changes. J. ophthalmol. 2017;1:20-4.
- Hudzʹ AS, Maksymtsiv ML. Funktsionalʹnyy stan trombotsytiv i porushennya mikrotsyrkulyatsiyi sitkivky u patsiyentiv, khvorykh na tsukrovyy diabet 2-ho typu. Arkhiv oftalʹmolohiyi Ukrayiny. 2017;2(8):27-32. [in Ukrainian].
- Hudzʹ AS, Maksymtsiv ML, Zyablitsev SV, Mohilevsʹkyy SYu. Protrombohennyy fenotyp trombotsytiv u patsiyentiv iz neproliferatyvnoyu diabetychnoyu retynopatiyeyu. Mizhnarodnyy endokrynolohichnyy zhurnal. 2018;14(2). DOI: http://dx.doi.org/10.22141/22240721.14.2.2018.130558 [in Ukrainian].
- Lally DR, Shah CP, Heier JS. Vascular endothelial growth factor and diabetic macular edema. Surv Ophthalmol. 2016;61(6):759-68.
- Italiano JE, Richardson JL, Patel-Hett S, Battinelli E, Zaslavsky A, Short S, et al. Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood. 2008;111(3):1227-33.
- Blum A, Socea D, Sirchan R. Vascular responsiveness in type 2 diabetes mellitus (T2DM). QJM. 2016;11: hcw081.
- van der Wijk AE, Hughes JM, Klaassen I, Van Noorden CJF, Schlingemann RO. Is leukostasis a crucial step or epiphenomenon in the pathogenesis of diabetic retinopathy? J Leukoc Biol. 2017;102(4):993-1001.
- Gómez-Moreno D, Adrover JM, Hidalgo A. Neutrophils as effectors of vascular inflammation. Eur J Clin Invest. 2018;23:e12940.
- Giles JA, Greenhalgh AD, Denes A, Nieswandt B, Coutts G, McColl BW, et alhttps://www.ncbi.nlm.nih.gov/pubmed/?term=Allan%20SM%5BA uthor%5D&cauthor=true&cauthor_uid=29325217. Neutrophil infiltration to the brain is platelet-dependent, and is reversed by blockade of platelet GPIbα. Immunology. 2018;154(2):322-8.
- Panicker SR, Mehta-D’souza P, Zhang N, Klopocki AG, Shao B, McEver RP. Circulating soluble P-selectin must dimerize to promote inflammation and coagulation in mice. Blood. 2017;130(2):181-91.
Publication of the article:
«Bulletin of problems biology and medicine» Issue 4 part 1 (146), 2018 year, 107-111 pages, index UDK 617.735-002-02:616.633.66+616.155.2]-076.5