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Diyabetik Retinopati ve Nitrik Oksit

Year 2015, Volume: 16 Issue: 1, 57 - 66, 08.05.2015
https://doi.org/10.18229/ktd.61071

Abstract

One of the most important cause of blindness in developed or developing countries is diabetic retinopathy, of which pathogenesis has not been yet clarified exactly. Understanding of pathogenesis of DRP can cause better management of this disease. Vascular damage is leading pathology in diabetic retinopathy. There is some proof that endothelin has important role in maintenance of vascular tonus and structure. Nitric oxide (NO) is one of the most important vasoactive mediators derived from endothelium. Nitric oxide is multifunctional molecule having key role on the anti-proliferative regulation of vascular smooth muscle cells. It has also been suggested that nitric oxide can play a role in the pathogenesis of diabetic retinopathy.There are three nitric oxide synthase (NOS) isoenzymes producing NO. Out of them, the isoenzyme present essentially in vascular endothelium is called as endothelialNOS (eNOS) and needed to protect endothelial functions. It has been reported that NO can control cellular growth and play role in the retinal pathologies due to proliferative retinal diseases. From this respect, eNOS appears to be an interesting molecule in the identification of microvascular complications of diabetes. Various polymorphisms have also been identified in the eNOS gene. The T-786C polymorphism located in promoter region of eNOS gene, 27-bp duplication in intron 4 region and Glu298Asp in exon 7 have been attracting attention. Defective retinal eNOS expression related to its polymorphisms may contribute to the development of macular edema. Differences among the studies may demonstrate that a relationship between diabetic retinopathy and eNOS gene polymorphism can vary due to geographic and ethnic differences. Importance of NO and relevant gene polymorphisms in the pathogenesis of diabetic retinopathy has been reviewed in this article

References

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Diyabetik Retinopati ve Nitrik Oksit

Year 2015, Volume: 16 Issue: 1, 57 - 66, 08.05.2015
https://doi.org/10.18229/ktd.61071

Abstract

Erişkin körlüğünün en önemli nedenlerinden birisi patogenezi tam olarak açıklanamamış diyabetik retinopatidir. Diyabetik retinopati patogenezinin anlaşılması daha iyi tedavisine ön ayak olabilir. Diyabetik retinopatide vasküler hasar ön plandadır. Endotelin vasküler tonus ve yapının korunmasında önemli rolü olduğuna ilişkin kanıtlar vardır. Endotel türevi vazoaktif mediatörlerden en önemlilerinden biri nitrik oksittir. Nitrik oksit vasküler düz kas hücrelerinin antiproliferatif düzenlenmesinde anahtar role sahip çok fonksiyonlu bir moleküldür. Diabetik retinopati patogenezinde nitrik oksitin de rolü olabileceği savunulmaktadır. Nitrik oksit sentezi yapan üç tür NOS izoenzimi vardır. Bunların içinden temel olarak vasküler endotelde bulunmakta olan izoenzim, endotelial-NOS (eNOS) olarak adlandırılır. eNOS endotel fonksiyonunun korunmasında gereklidir . Retinanın proliferatif hastalıklarında nitrik oksidin rolü olabileceği, nitrik oksidin hücre büyümesini kontrol edebileceği bildirilmiştir. Bu açıdan diyabetin mikrovasküler komplikasyonlarının belirlenmesinde eNOS ilgi çekici görünmektedir. eNOS geninde çeşitli polimorfizmler tanımlanmıştır. Özellikle promotor bölgesindeki T-786C, 4. intron bölgesinde 27-bp tekrarı ve 7. eksondaki Glu298Asp dikkat çekmiştir. Endoteliyal NOS gen polimorfizm ile ilgili olarak retinadaki defektif eNOS ekspresyonu özellikle diabetik makula ödemi gelişimine katkıda bulunabilmektedir. Çalışmalardaki farklılıklar diyabetik retinopati ile eNOS gen polimorfizmi arasındaki ilişkinin coğrafik ve etnik farklılıklara göre değişebildiğini göstermektedir. Bu makalede NO ve ilgili gen polimorfizmlerinin diabetik retinopati patogenezindeki önemi gözden geçirilmeye çalışılmıştır

References

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  • Cerillo A, Bortolotti N, Motz E, Crescetini A, Lizzio S.,Russo A, Tonutti L, Taboga C. Meal-generated oxidative stress in type 2 diabetic patients. Diabetes Care 1998;21:1529-1533.
  • Becquet F, Courtois Y, Goyreau O. Nitric oxide in the eye: multifaceted roles and diverse outcomes. Surv Ophtalmol 1997;42:71-82.
  • Shimizu K, Wu GS, Sultana C, Karla VK, Rao NA. Stimulation of macrophages by retinal proteins: production of reactive nitrogen and oxygen metabolites. Invest Ophthalmol Vis Sci 1999;40:3215-3223.
  • Böger RH. The emerging role of asymmetric dimethylarginine as a novel cardiovascular risk factor. Cardiovasc Res 2003;59:824-833.
  • Böger RH, Bode-Böger SM, Szuba A, Tangphao O, Tsao PS, Chan JR et al. Asymmetric dimethylarginine: a novel risk factor for endothelial dysfunction. Its role in hypercholesterolemia. Circulation 1998;98:1842–1847.
  • Nadaud S, Bonnardeaux A, Lathrop M, Soubrier F. Gene structure, polymorphism and mapping of the human endothelial nitric oxide synthase gene. Biochem Biophys Res Commun 1994;198:1027-1033.
  • Waldman SA, Murad F. Biochemical mechanisms underlying vascular smooth muscle relaxation: the guanylate cyclase- cyclic GMP system. J Cardiovasc Pharmacol 1988;12(Suppl 5) :15-18.
  • Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and macular edema: pathophysiology, screening, and novel therapies. Diabetes Care 2003;26:2653-2664.
  • Antcliff RJ, Marshall J. The pathogenesis of edema in diabetic maculopathy. Semin Ophtalmol 1999;14:223-232.
  • Pelzek C, Lim JI. Diabetic macular edema: review and update. Ophtalmol Clin North Am 2002;15:555-563.
  • Gross SS, Wolin MS: Nitric oxide: pathophysiological mechanisms. Annu Rev Physiol 1195;57:737-769.
  • Albrecht EW, Stegeman Ca, Heeringa P, Henning RH, van Goor H. Protective role of endothelial nitric oxide synthase. J Pathol 2003;199:8-17.
  • Miyamoto Y, Saito Y, Kajiyama N, et al. Endothelial nitric oxide synthase gene is positively associated with essential hypertension. Hypertension 1998;32:3-8.
  • Nakayama M, Yasue H, Yoshimura M, et al. T-786-C mutation in the 5’-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 1999;99 :2864-2870.
  • Taverna MJ, Sola A, Guyot-Argenton C, Pacher N, Bruzzo F, Chevalier A, Slama G,Reach G, Selam JL. eNOS4 polymorphism of the endothelial nitric oxide synthase predicts risk for severe diabetic retinopathy. Diabet Med 2002;19:240-245.
  • Frost D, Chitu J, Meyer M, Beischer W, Pfohl M. Endothelial nitric oxide synthase (ecNOS) 4 a/b gene polymorphism and carotid artery intima- media thickness in type 1 diabetic patients. Exp Clin Endocrinol Diabetes 2003 ;111:12-15.
  • Takuya A, Tamotsu N, Hiroyuki I, et al. Endothelial nitric oxide synthase gene is associated with diabetic macular edema in type 2 diabetes. Diabetes Care 2004; 27:2184-2190.
  • Kröncke KD, Feshel K., Kolb-Bachofen V. Inducible nitric oxide synthase and its product nitric oxide, a small molecule with complex biological activities. Biol Chem 1995;376 (Supll):327-343.
  • Ahmad I, Leinders-Zufall T, Kocsis JD. Retinal ganglion cells express a cGMP-gate cation concouctance activitable by nitric oxide donors. Neuron 1994;12:155-165.
  • Stamler JS..Redox signaling: Nitrosylation and related target interactions of nitric oxide. Cell 1994;78:931-936
  • Tilton RG, Chang K, Corbett JA., Misko TP, Currie MG, Bora NS, Kaplan HJ, Williamson JR. Endotoxin- induced üveitis in the rat in attenuated by inhibition of nitric oxide production. Invest Ophthalmol Vsi Sci 1994;35:3278-3288.
  • Becquet F, Courtois Y, Goureau O. Nitric oxide decreases in vitro phagocytosis of photoreceptor outer segments by bovine retinal pigmented epithelial cells. J Cell Physiol 1994;159:259-262.
  • Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373-376.
  • Rapoport RM, Murad F. Agonist-induced endothelium- dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res 1983;52:352-357.
  • Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Bloch KD. Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem 1992;267:14519-14522.
  • Shinde UA, Mehta AA, Goyal RK. Nitric oxide: A molecule of the millennium. Indian J Exp Biol 2000;38:201-210.
  • Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J 2001;357:593-615.
  • Govers R, Rabelink TJ. Cellular regulation of endothelial nitric oxide synthase. Am J Physiol 2001;280:193-206.
  • Warpeha KM, Xu W, Liu L, et al. Genotyping and functional analysis of a polymorphic (CCTTT) (n) repeat of NOS2A in diabetic retinopathy. FASEB J 1999; 13:1825-1832.
  • The Diabetes Control and Complications Trial Research Group. Clustering of long-term complications in families with diabetes in the Diabetes Control and Complications Trial. Diabetes 1997;46:1829-1839
  • Vailance P, Collier J. Biology and ciinical relevance of nitric oxide. Br Med J 1994; 309:453-457.
  • Ziche M. Role of nitric oxide in the angiogenesis of avascular tissue. Osteoarthritis Cartilage 1999;7:403- 405.
  • Monti LD, Valsecchi G, Costa S, et al. Effects of endothelin-l and nitric oxide on glucokinase activity in isolated rat hepatocytes. Metabolism 2000;49:73 -78
  • Piatti PM, Monti LD, Zavaroni I, et al. Alterations in nitric oxide/cyclic-GMP pathway in nondiabetic siblings of patients with type 2 diabetes. J Clin Endocrinol Metab 2000;85:2416-2420.
  • Wang XL, Mahaney MC, Sim AS, et al. Genetic contributıon of endothelial constitutive nitric oxide synthase gene to plasma nitric oxide levels. Arterioscler Thromb Vasc Biol 1997;17:3147-3153.
  • Tsukada T, Yokoyama K, Arai T, et al. Evidence of assocıation of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. Biochem Bıophys Res Commun 1998;245:190-193.
  • Do Carmo A, Lopes C, Santos M, Proenca R, Cunha- Vaz J. Carvalho AP. Nitric oxide synthase activity and L-arginine metabolism in the retinas from streptozotocin-induced diabetic rats. Gen Pharmacol 1998;30:319-324.
  • Martin AR, Bailie JR, Robson T, et al. Retinal pericytes control expression of nitric oxide synthase and endothelin 1 in microvascular endothelial celis. Microvasc Res 2000;59:131-139.
  • Schmetterer L, Findl O, Fasching P, et al. Nitric oxide and ocular blood flow in patients with IDDM. Diabetes 1997;46:653-659.
  • Du Y.,Sarthy VP, Kern TS. Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats. Am. J. Physiol Regul Integr Comp Physiol 2004;287(4) :735-741
  • Kumaramanickavel G, Sripriya S, Vellanki RN, Upadyay NK, Badrinath SS, Rajendran V, Sukumar B, Ramprasad VL, Sharma T. Inducible nitric oxide synthase gene and diabetic retinopathy in Asian Indian patients. Ciinical Genetics 2002;61:344-348.
  • Tesauro M, Thompson WC, Rogliani P, Qi L, Chaudhary PP, Moss J. lntracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins wıth aspartate vs. glutamate at position 298. Proc Natl Acad Sci 2000;97:2832-2835.
  • Chan NN, Vallance P, Colhoun HM. Nitric oxide and vascular responses in type 1 diabetes. Diabetologia 2000;43:137-147
  • Klein R. Klein BE, Moss SE, Davis MD, De Mets DL. The Wisconsin epidemiologic study of diabetic retinopathy II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol 1984;102:520-526.
  • Shibuki H, Katai N, Yodoi J. Uchida K. Yoshimura N. Lipid peroxidation and peroxynitrite in retinal ischemia-reperfusion injury. Invest Ophthalmol Vis Sci 2000;41:3607-3614.
  • Hartnett ME, Stratton RD, Browne RW, Rosner BA, Lanham RJ, Armstrong D. Serum markers of oxidative stress and severity of diabetic retinopathy. Diabetes Care 2000;23:234-240.
  • Tilton RG, Chang KC, LeJeune WS, Stephan CC, Brock TA, Williamson JR. Role for nitric oxide in the hyperpermeability and hemodynamic changes induced by intravenous VEGF. Invest Ophthalmol Vis Sci 1999;40:689-696.
  • Brooks SE, Gu X, Samuel S, Marcus DM, Bartoli M, Huang PL et al. Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice. Invest Ophthalmol Vis Sci 2001;42:222-228.
  • Sennlaub F, Courtois Y, Goureau O. Inducible nitric oxide synthase mediates the change from retinal to vitreal neovascularization in ischemic retinopathy. J Clin Invest 2001;6:717-725.
  • Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 1991;88:4651-4655.
  • Miyamoto K, Ogura Y: Pathogenetic potential of leukocytes in diabetic retinopathy. Semin Ophthalmol 1999;14:233-239.
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There are 77 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Sibel İnan This is me

Publication Date May 8, 2015
Published in Issue Year 2015 Volume: 16 Issue: 1

Cite

APA İnan, S. (2015). Diyabetik Retinopati ve Nitrik Oksit. Kocatepe Tıp Dergisi, 16(1), 57-66. https://doi.org/10.18229/ktd.61071
AMA İnan S. Diyabetik Retinopati ve Nitrik Oksit. KTD. April 2015;16(1):57-66. doi:10.18229/ktd.61071
Chicago İnan, Sibel. “Diyabetik Retinopati Ve Nitrik Oksit”. Kocatepe Tıp Dergisi 16, no. 1 (April 2015): 57-66. https://doi.org/10.18229/ktd.61071.
EndNote İnan S (April 1, 2015) Diyabetik Retinopati ve Nitrik Oksit. Kocatepe Tıp Dergisi 16 1 57–66.
IEEE S. İnan, “Diyabetik Retinopati ve Nitrik Oksit”, KTD, vol. 16, no. 1, pp. 57–66, 2015, doi: 10.18229/ktd.61071.
ISNAD İnan, Sibel. “Diyabetik Retinopati Ve Nitrik Oksit”. Kocatepe Tıp Dergisi 16/1 (April 2015), 57-66. https://doi.org/10.18229/ktd.61071.
JAMA İnan S. Diyabetik Retinopati ve Nitrik Oksit. KTD. 2015;16:57–66.
MLA İnan, Sibel. “Diyabetik Retinopati Ve Nitrik Oksit”. Kocatepe Tıp Dergisi, vol. 16, no. 1, 2015, pp. 57-66, doi:10.18229/ktd.61071.
Vancouver İnan S. Diyabetik Retinopati ve Nitrik Oksit. KTD. 2015;16(1):57-66.

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