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Diyabetik Retinopati ve Nitrik Oksit

Yıl 2015, Cilt: 16 Sayı: 1, 57 - 66, 08.05.2015
https://doi.org/10.18229/ktd.61071

Öz

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

Kaynakça

  • Smiddy WE, Flynn HW. Vitrectomy in the management of diabetic retinopathy. Surv Ophtalmol 1999;43:491-507.
  • 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.
  • Kubes P, Granger DN. Nitric oxide modulates microvascular permeability. Am J Physiol 1992;262:611- 615.
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  • Taverna MJ, Elgrably F, Selmi H, Selam JL. The T-786C and C774T endothelial nitric oxide synthase gene polymorphisms independently affect the onset pattern of severe diabetic retinopathy. Nitric Oxide 2005;13:88-92.
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Diyabetik Retinopati ve Nitrik Oksit

Yıl 2015, Cilt: 16 Sayı: 1, 57 - 66, 08.05.2015
https://doi.org/10.18229/ktd.61071

Öz

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

Kaynakça

  • Smiddy WE, Flynn HW. Vitrectomy in the management of diabetic retinopathy. Surv Ophtalmol 1999;43:491-507.
  • 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.
  • Kubes P, Granger DN. Nitric oxide modulates microvascular permeability. Am J Physiol 1992;262:611- 615.
  • He P, Zeng M, Curry FE. Effect of nitric oxide synthase inhibitors on basal microvessel permeability and endothelial cell (Ca2+)i. Am J Physiol 1997;273:747- 755.
  • Haverkamp S, KoIb H. Cuenca N. Endothelial nitric oxide synthase (eNOS) is localized to Muller cells in all vertebrate retinas. Vision Res 1999;39:2299-2303.
  • Awata T, Neda T, Iizuka H, Kurihara S, Ohkubo T, Takata N, Osaki M, Watanabe M, Nakashima Y, Sawa T, Inukai K, Inoue I, Shibuya M, Mori K, Yoneya S, Katayama S. Endothelial nitric oxide synthase gene is associated with diabetic macular edema in type 2 diabetes. Diabetes Care 2004;27:2184-2190.
  • Taverna MJ, Elgrably F, Selmi H, Selam JL. The T-786C and C774T endothelial nitric oxide synthase gene polymorphisms independently affect the onset pattern of severe diabetic retinopathy. Nitric Oxide 2005;13:88-92.
  • Cai H, Wang X, Colagiuri S, Wilcken DEL. A common Glu298Asp (894G-T) mutation at exon 7 of the endothelial nitric oxide synthase gene and vascular complications in type 2 diabetes. Diabetes Care 1998;21:2195.
  • Tso AW, Tan KC, Wat NM, Janus ED, Lam TH, S L Lam K. Endothelial nitric oxide synthase G894T (Glu298Asp) polymorphism was predictive of glycemic status in a 5-year prospective study of Chinese subjects with impaired glucose tolerance. Metabolism 2006;55:1155- 1158.
  • Spinas GA. The dual role of nitric oxide in islet ß-ceIls. N Physiol Sci 1999;14: 49-54.
  • Kobzik L, Stringer B, Balligand JL, Reid MB, Stamler JS. Endothelial type nitric oxide synthase in skeletal muscle fibers: mitochondrial relationships. Biochem Biophys Res Commun 1995;211:375-381.
  • Baron AD, Zhu JS, lrsula 0, Brechtel G, Keech C. Insulin resistance after hypertension induced by the nitric oxide synthesis inhibitor L-NMMA in rats. Am J Physiol Endocrinol Metab 1995;269:709-715.
  • Piatti PM, Monti LD, Zavaroni I, Valsecchi G, Van Phan C, Costa S, Conti M Sandoli EP, Solerte B, Pozza G, Pontiroli AE, Reaven G: Alteration in Nitric oxide/cycling-GMP pathway in nondiabetic siblings of patients with type 2 diabetes. J Clin Endocrinol Metab 2000;85:2416-2420.
  • Zavaroni I, Piatti PM, Monti LD, Gasparini P, Barilli LA, Massironi P, Ardigo D, Valsecchi G, Delsignore R, Raven GM. Plasma nitric oxide concentrations are elevated in insulin resistant healthy subjects. Metabo ism 2000;49:959-961.
  • Ukkola O, Erkkila PH, Savolainen MJ, Kesaniemi YA. Lack of association between polymorphism of catalase, copper-zinc superoxide dismutase (SOD), extracellular SOD and endothelial nitric oxide synthase genes and macroangiopathy in patients with type 2 diabetes mellitus. J Int Med 2001 ;249: 451-459.
  • Patel A, Hibberd ML, Millward BA, Demaine AG. Chromosome 7q35 and susceptibility to diabetic microvascular complications. J Diabetes Complications 1996;10:62-67.
  • Neugebauer S, Baba T, Watanabe T. Association of the nitric oxide synthase gene polymorphism with an increased risk for progression to diabetic nephropathy in type 2 diabetes. Diabetes 2000;49:500-503.
  • Zanchi A, Moczulski DK, Hanna LS, Wantman M, Warram JH, Krolewski AS. Risk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism. Kidney Int 2000;57:405-413.
  • Weekers L, Hadjadj S, Belloum R, Gallois Y, Bouhanick B, Marre M. Lack of contribution of two endothelial nitric oxide synthase (eNOS) gene polymorphisms to diabetic nephropathy in type 1 diabetes. Diabetologia 1999;42:266.
  • Warpeha KM, Ah-Fat F, Harding S, Patterson CC, Xu W, Hart PM et al. Dinucleotide repeat polymorphisms in EDN1 and NOS3 are not associated with severe diabetic retinopathy in type 1 or type 2 diabetes. Eye 1999;13:174-178.
  • Tavakkoly-Bazzaz J, Boulton AJM, Pravica V, Hutchinson IV. eNOS gene
  • polymorphism in type 1 diabetes and its microangiopathic complications. Diabetes Metab 2003;29(Suppl2):S42.
  • Chen Y, Huang H, Zhou J, et al. Polymorphism of the endothelial nitric oxide synthase gene is associated with diabetic retinopathy in a cohort of West Africans. Mol Vis 2007;13:2142-2147.
  • Santos KG,Crispim D, Canani LH, et al. Relationship of endothelial nitric oxide synthase ( eNOS) gene polymorphisms with diabetic retinopathy in Caucasians with type 2 diabetes. Ophtalmic Genetics,2012;33(1) :23-27.
  • Cilensek I,Mankoc S,Petrovic MG, et al. The 4a/4a genotype of the VNTR polymorphism for endothelial nitric oxide synthase (eNOS) gene predicts risk for proliferative diabetic retinopathy in Slovenian patients ( Caucasians) with type 2 diabetes mellitus. Mol Biol Rep,2012
  • Suganthalakshmi B, Anand R, Kim R, et al. Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. Mol Vis 2006;12:336-341.
  • Uthra S, Raman R, Mukesh BN,et al. Intron 4 VNTR of endothelial nitric oxide synthase (eNOS) gene and diabetic retinopathy in type 2 patients in southern India. Ophtalmic Genet 2007;28:77-81.
Toplam 77 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Makaleler-Araştırma Yazıları
Yazarlar

Sibel İnan Bu kişi benim

Yayımlanma Tarihi 8 Mayıs 2015
Yayımlandığı Sayı Yıl 2015 Cilt: 16 Sayı: 1

Kaynak Göster

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. Nisan 2015;16(1):57-66. doi:10.18229/ktd.61071
Chicago İnan, Sibel. “Diyabetik Retinopati Ve Nitrik Oksit”. Kocatepe Tıp Dergisi 16, sy. 1 (Nisan 2015): 57-66. https://doi.org/10.18229/ktd.61071.
EndNote İnan S (01 Nisan 2015) Diyabetik Retinopati ve Nitrik Oksit. Kocatepe Tıp Dergisi 16 1 57–66.
IEEE S. İnan, “Diyabetik Retinopati ve Nitrik Oksit”, KTD, c. 16, sy. 1, ss. 57–66, 2015, doi: 10.18229/ktd.61071.
ISNAD İnan, Sibel. “Diyabetik Retinopati Ve Nitrik Oksit”. Kocatepe Tıp Dergisi 16/1 (Nisan 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, c. 16, sy. 1, 2015, ss. 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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