MOLECULAR MECHANISMS OF PATHOGENESIS OF DIABETIC RETINOPATHY
Keywords:diabetic retinopathy, pathogenesis, molecular mechanisms, adhesion molecules
An overview of current researches regarding the pathogenesis of a diabetic retinopathy was made. The role of following molecules were described: family of selectin molecules (P-, E- and L-selectin), which is responsible for rolling of leukocytes along the endothelial cells; molecules that mediate strong adhesion – ICAM-1 (intercellular adhesion molecule), VCAM-1 (vascular adhesion molecule) and molecules involved in transmigration of white blood cells: PECAM-1 (platelet-endothelial adhesion molecules), JAM (junctional adhesion molecules) and VAP 1 (vascular adhesion protein-1). The study of the molecular mechanisms of infl ammation is very perspective to determine the objective biomarkers of infl ammation, make disease’s prognosis and develop treatment strategies.
IDF Diabetes Atlas 7th Edition [Electronic resource]. – Way of acces: http://www.idf.org/idf-diabetes-atlas-seventh-edition. – Title from the screen.
Kertes P. J. Evidence Based Eye Care / P. J. Kertes, T. M. Johnson // Lippincott Williams & Wilkins. – 2007. – P. 6964–6967.
Prokofyeva E. Epidemiology of major eye diseases leading to blindness in Europe: a literature review /E. Prokofyeva, E. Zrenner // Ophthalmic Res. – 2012. – Vol. 47, № 4. – P. 171–188.
Yau J. W. Meta-Analysis for Eye Disease (META - EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy / J. W. Yau, S. L. Rogers, R. Kawasaki [et al.] // Diabetes Care. – 2012. – Vol. 35, № 3. – P. 556–564.
Xu H. Para-infl ammation in the aging retina / H. Xu, M. Chen, J. V. Forrester // Progress in Retinal and Eye Research. – 2009. – Vol. 28, № 5. – P. 348–368.
Adamis A. P. Immunological mechanisms in the pathogenesis of diabetic retinopathy / A. P. Adamis, A. J. Berman // Seminars in Immunopathology. – 2008. – Vol. 30, № 2. – P. 65–84.
Antonetti D. A. Diabetic retinopathy: seeing beyond glucose-induced microvascular disease / D. A. Antonetti, A. J. Barber, S. K. Bronson [et al.] // Diabetes. – 2006. – Vol. 55, № 9. – P. 2401–2411.
Gross J. G. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: A randomized clinical trial. Writing Committee for the Diabetic Retinopathy Clinical Research Network / J. G. Gross, A. R. Glassman, L. M. Jampol [et al.] // JAMA. – 2015. – Vol. 314. – P. 2137–2146.
Bevilacqua M. P. Endothelial-leukocyte adhesion molecules / M. P. Bevilacqua // Ann Rev Immunology. – 1993. – Vol. 11. – P. 767–804.
Lutty G. A. Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid / G. A. Lutty, J. Cao, D. S. McLeod // American Journal of Pathology. – 1997. – Vol. 151, № 3. – P. 707–714.
Kim S. Y. Neutrophils are associated with capillary closure in spontaneously diabetic monkey retinas /S. Y. Kim, M. A. Johnson, D. S. McLeod [et al.] //Diabetes. – 2005. – Vol. 54, № 5. – P. 1534–1542.
Joussen A. M. Suppression of Fas-FasL-induced endothelial cell apoptosis prevents diabetic bloodre tinal barrier breakdown in a model of streptozotocin-induced diabetes / A. M. Joussen, V. Poulaki, N. Mitsiades [et al.] // The FASEB Journal. – 2003. – Vol. 17, № 1. – P. 76–78.
Kase S. Proliferative diabetic retinopathy with lymphocyte-rich epiretinal membrane associated with poor visual prognosis / S. Kase, W. Saito, S. Ohno, S. Ishida // Investigative Ophthalmology & Visual Science. – 2009. – Vol. 50, № 12. – P. 5909–5912.
Ley K. Functions of selectins / K. Ley // Results and Problems in Cell Differentiation. – 2001. – Vol. 33. – P. 177–200.
Kaneider N. C. Therapeutic targeting of molecules involved in leukocyte-endothelial cell interactions /N. C. Kaneider, A. J. Leger, A. Kuliopulos // FEBS Journal. – 2006. – Vol. 273, № 19. – P. 4416–4424.
McEver R. P. Selectins: lectins that initiate cell adhesion under fl ow / R. P. McEver // Current Opinion in Cell Biology. – 2002. – Vol. 14, № 5. – P. 581–586.
McLeod D. S. Enhanced expression of intracellular adhesion molecule-1 and P-selectin in the diabetic human retina and choroid / D. S. McLeod, D. J. Lefer, C. Merges, G. A. Lutty // American Journal of Pathology. – 1995. – Vol. 147, № 3. – P. 642–653.
Adamiec-Mroczek J. Proliferative diabetic retinopathy – the infl uence of diabetes control on the activation of the intraocular molecule system / J. Adamiec-Mroczek, J. Ofi cjalska-Młyńczak, M. Misiuk-Hojło // Diabetes Research and Clinical Practice. – 2009. – Vol. 84, № 1. – P. 46–50.
Limb G. A. Vascular adhesion molecules in vitreous from eyes with proliferative diabetic retinopathy /G. A. Limb, J. Hickman-Casey, R. D. Hollifi eld, A. H. Chignell // Investigative Ophthalmology and Visual Science. – 1999. – Vol. 40, № 10. – P. 2453–2457.
Mastej K. Neutrophil surface expression of CD11b and CD62L in diabetic microangiopathy / K. Mastej, R. Adamiec // Acta Diabetologica. – 2008. – Vol. 45, № 3. – P. 183–190.
Guaiquil V. H. ADAM8 is a negative regulator of retinal neovascularization and of the growth of heterotopically injected tumor cells in mice / V. H. Guaiquil, S. Swendeman, W. Zhou [et al.] // Journal of Molecular Medicine. – 2010. – Vol. 88, № 5. – P. 497–505.
Scheller J. ADAM17: a molecular switch to control infl ammation and tissue regeneration / J. Scheller, A. Chalaris, C. Garbers, S. Rose-John // Trends in Immunology. – 2011. – Vol. 32, № 8. – P. 380–387.
Gómez-Gaviro M. Expression and regulation of the metalloproteinase ADAM-8 during human neutrophil pathophysiological activation and its catalytic activity on L-selectin shedding / M. Gómez-Gaviro, M. Domínguez-Luis, J. Canchado [et al.] // Journal of Immunology. – 2007. – Vol. 178, № 12. – P. 8053–8063.
Noda K. Leukocyte Adhesion Molecules in Diabetic Retinopathy / K. Noda, N. Shintaro, I. Susumu, I. Tatsuro // Journal of Ophthalmology. – 2012. – P. 6. – Article ID 279037.
Matsumoto K. Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy / K. Matsumoto, Y. Sera, Y. Ueki [et al.] // Diabetic Medicine. – 2002. – Vol. 19, № 10. – P. 822–826.
Spijkerman A. M. Endothelial dysfunction and lowgrade infl ammation and the progression of retinopathy in Type 2 diabetes / A. M. Spijkerman, M. A. Gall, L. Tarnow [et al.] // Diabetic Medicine. – 2007. – Vol. 24, № 9. – P. 969–976.
Olson J. A. Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration / J. A. Olson, C. M. Whitelaw, K. C. McHardy [et al.] // Diabetologia. – 1997. – Vol. 40, № 10. – P. 1166–1171.
Gustavsson C. TNF-α is an indepedent serum marker for proliferative retinopathy in type 1 diabetic patients / C. Gustavsson, E. Agardh, B. Bengtsson, C. D. Agardh // Journal of Diabetes and its Complications. – 2008. – Vol. 22, № 5. – P. 309–316.
Hogg N. The insider’s guide to leukocyte integrin signalling and function / N. Hogg, I. Patzak, F. Willenbrock // Nature Reviews Immunology. – 2011. – Vol. 11, № 6. – P. 416–426.
Heidenkummer H. P. Intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) expression in human epiretinal membranes / H. P. Heidenkummer, A. Kampik //Graefe’s Archive for Clinical and Experimental Ophthalmology. – 1992. – Vol. 230, № 5. – P. 483–487.
Lutty G. A. Effects of diabetes on the eye / G. A. Lutty // Invest Ophthalmol Vis Sci. – 2013. – Vol. 54, № 14. – P.81–87.
Song H. Expression of CD18 on the neutrophils of patients with diabetic retinopathy / H. Song, L. Wang, Y. Hui // Graefe’s Archive for Clinical and Experimental Ophthalmology. – 2007. – Vol. 245, № 1. – P. 24–31.
Zhu Q. CD18 expression in granulocytes infi ltrating the vitreous fl uid in patients with diabetic retinopathy / Q. Zhu, H. P. Song // Int J Ophthalmol. – 2015. – Vol. 8, № 3. – P. 508–512.
Kociok N. ICAM-1 depletion does not alter retinal vascular development in a model of oxygen-mediated neovascularization / N. Kociok, S. Radetzky, T. U. Krohne [et al.] // Experimental Eye Research. – 2009. – Vol. 89, № 4. – P. 503–510.
Ulbrich H. Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions in infl ammatory disease / H. Ulbrich, E. E. Eriksson, L. Lindbom // Trends in Pharmacological Sciences. – 2003. – Vol. 24, № 12. – P. 640–647.
Wautier J. L. Blood cells and vascular cell interactions in diabetes / J. L. Wautier, M. P. Wautier // Clinical Hemorheology and Microcirculation. – 2001. – Vol. 25, № 2. – P. 49–53.
Gustavsson C. Vascular cellular adhesion molecule-1 (VCAM-1) expression in mice retinal vessels is affected by both hyperglycemia and hyperlipidemia /C. Gustavsson, C. D. Agardh, A. V. Zetterqvist [et al.] // PLoS One.– 2010. – Vol. 5, № 9. – P. 1–12. – Article ID e12699.
Koch A. E. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1 /A. E. Koch, M. M. Halloran, C. J. Haskell [et al.] //Nature. – 1995. – Vol. 376, № 6540. – P. 517–519.
Eshaq R. S. The Role of Matrix Metalloproteinases (MMPs) in Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) Lossin Diabetic Retinopathy: In Vivo and in Vitro Studies / R. S. Eshaq, N. Harris //Molecular and Cellular Physiology. – 2016. – Vol. 30, № 1. – P. 950–957.
Loukovaara S. Indications of lymphatic endothelial differentiation and endothelial progenitor cell activation in the pathology of proliferative diabetic retinopathy / S. Loukovaara, E. Gucciardo, P. Repo [et al.] // Acta Ophthalmol. – 2015. – Vol. 93, № 6. –P. 512–523.
Ebnet K. Junctional adhesion molecules (JAMs): more molecules with dual functions? / K. Ebnet, A. Suzuki, S. Ohno, D. Vestweber // Journal of Cell Science. – 2004. – Vol. 117. – P. 19–29.
Palmeri D. Vascular endothelial junction-associated molecule, a novel member of the immunoglobulin superfamily, is localized to intercellular bound aries of endothelial cells / D. Palmeri, A. van Zante, C. C. Huang [et al.] // J. Biol. Chem. – 2000. – Vol. 275. – P. 19139–19145.
Ostermann G. JAM-1 is a ligand of the beta (2) integrin LFA-1 involved in transendothelial migration of leukocytes / G. Ostermann, K. S. Weber, A. Zernecke [et al.] // Nat. Immunol. – 2002. – Vol. 3. – P. 151–158.
Cunningham S. A. JAM2 interacts with alpha-4 beta-1. Facilitation by JAM3 / S. A. Cunningham, J. M. Rodriguez, M. P. Arrate [et al.] // J. Biol. Chem. – 2002. – Vol. 277. – P. 27589–27592.
Santoso S. The junctional adhesion molecule 3 (JAM-3) on human platelets is a counter receptor for the leukocyte integrin Mac-1 / S. Santoso, U. J. Sachs, H. Kroll [et al.] // J. Exp. Med. – 2002. – Vol. 196. – P. 679–691.
Orlova V. V. Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin-mediatedcell-cellcontacts / V. V. Orlova, M. Economopoulou, F. Lupu [et al.] // J Exp. Med. – 2006. – Vol. 203, № 12. – P. 2703–2714.
Economopoulou M. Endothelial-specifi c defi ciency of Junctional Adhesion Molecule-C promotes vessel normalisation in proliferative retinopathy / M. Economopoulou, N. Avramovic, A. Klotzsche-von Ameln [et al.] // Thromb Haemost. – 2015. – Vol. 114, № 6. – P. 1241–1249.
Joussen A. M. Leukocyte-mediated endothelial cell injury and death in the diabetic retina / A. M. Joussen, T. Murata, A. Tsujikawa [et al.] // American Journal of Pathology. – 2001. – Vol. 158, № 1. – P. 147–152.
Jaakkola K. Vascular adhesion protein-1, intercellular adhesion molecule-1 and P-selectin mediate leukocyte binding to ischemic heart in humans / K. Jaakkola, S. Jalkanen, K. Kaunismäki [et al.] // Journal of the American College of Cardiology. – 2000. – Vol. 36, № 1. – P. 122–129.
Singh B. Expression of vascular adhesion protein-1 in normal and infl amed mice lungs and normal human lungs / B. Singh, T. Tschernig, M. Van Griensven [et al.] // Virchows Archiv. – 2003. – Vol. 442, № 5. – P. 491–495.
Almulki L. Localization of vascular adhesion protein-1 (VAP-1) in the human eye / L. Almulki, K. Noda, S. Nakao [et al.] // Experimental Eye Research. – 2010. – Vol. 90, № 1. – P. 26–32.
Noda K. Vascular adhesion protein-1 regulates leukocyte transmigration rate in the retina during diabetes / K. Noda, S. Nakao, S. Zandi [et al.] // Experimental Eye Research. – 2009. – Vol. 89, № 5. – P. 774–781.
Garpenstrand H. Elevated plasma semicarbazide-sensitive amine oxidase (SSAO) activity in Type 2 diabetes mellitus complicated by retinopathy / H. Garpenstrand, J. Ekblom, L. B. Bäcklund [et al.] // Diabetic Medicine. – 1999. – Vol. 16, № 6. – P. 514–521.
Grönvall-Nordquist J. L. Follow-up of plasma semicarbazide-sensitive amine oxidase activity and retinopathy in Type 2 diabetes mellitus / J. L. Grönvall-Nordquist, L. B. Bäcklund, H. Garpenstrand [et al.] // Journal of Diabetes and its Complications. – 2001. – Vol. 15, № 5. – P. 250–256.
Smith D. J. Targeting vascular adhesion protein-1 to treat autoimmune and infl ammatory diseases / D. J. Smith, P. J. Vainio // Annals of the New York Academy of Sciences. – 2007. – Vol. 1110. – P. 382–388.
Bourajjaj M. Role of methylglyoxal adducts in the development of vascular complications in diabetes mellitus / M. Bourajjaj, C. D. Stehouwer, V. W. Van Hinsbergh, C. G. Schalkwijk // Biochemical Society Transactions. – 2003. – Vol. 31, № 6. – P. 1400–1402.
Zong H. AGEs, RAGE and diabetic retinopathy /H. Zong, M. Ward, A.W. Stitt // Current Diabetes Reports. – 2011. – Vol. 11, № 4. – P. 244–252.
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