Pathogenesis of diabetic retinopathy

Česká verzia

Authors: T. Pelikánová
Authors place of work: Centrum diabetologie Institutu klinické a experimentální medicíny, Praha, přednosta prof. MUDr. Terezie Pelikánová, DrSc.
Published in the journal: Vnitř Lék 2007; 53(5): 498-505
Category:

Předneseno na 8. celostátním diabetologickém symposiu „Diabetes a další obory II (smyslové ústrojí a pohybová aktivita)“ ve dnech 2. - 3. června 2006 v Novém Adalbertinu v Hradci Králové

Summary

Diabetic retinopathy (DR) develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. The main risk factor of DR is hyperglycemia accompanied by enhanced mitochondrial production of reactive oxygen species and oxidative stress, formation of advanced glycation end products (AGE) and hexosamines, increased polyol metabolism of glucose. The severity of vascular injury depends on the individual genetic background and is modified by other metabolic and haemodynamic factors influencing numbers of intracellular signalling molecules such as PKC, MAPK or NF-κB. In diabetes, damage to the retina occurs in the vasculature (endothelial cells and pericytes), neurons and glia, pigment epithelial cells and infiltrating immunocompetent cells: monocytes, granulocytes, lymfocytes. These activated cells change the production pattern of a number of mediators such as growth factors, vasoactive agents, coagulation factors and adhesion molecules resulting in increased blood flow, increased capillary permeability, proliferation of extracellular matrix and thickening of basal membranes, altered cell turnover (apoptosis, proliferation, hypertrophy), procoagulant and proaggregant patterns, and finally in angiogenesis and tissue remodelling. The insights into pathophysiological mechanisms responsible for DR that are presented here could help in the development of a more targeted approach to its prevention and treatment.

Key words:
diabetic retinopathy – hyperglycemia – oxidative stress – hexosamine – advanced glycation end products

Zdroje

1. Aiello LP Angiogenic pathways in diabetic retinopathy. N Engl J Med 2005; 353: 839-841.

2. Ambati J, Chalam KV, Chawla DK et al. Elevated gamma-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy. Arch Ophthalmol 1997; 115: 161-166.

3. Beltramo E, Buttiglieri S, Pomero F et al. A study of capillary pericyte viability on extracellular matrix produced by endothelial cells in high glucose. Diabetologia 2003; 46: 409-415.

4. Bendlová B Komentář k článku: Yang B, Cross DF (2003): Polymorphism of the vascular endothelial growth factor and susceptibility to diabetic microvascular complications in patients with type 1 diabetes mellitus. Journal of Diabetes and Complication (české vydání) 2003; 1: 226-228.

5. Boehm BO, Lang G, Volpert O et al. Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy. Diabetologia 2003; 46: 394-400.

6. Colhoun HM, Betteridge DJ, Durrington PN et al. CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685-696.

7. DCCT Research Group. The effect of intensive diabetes treatment on the development and progression of long-term complication in insulin-dependent diabetes mellitus. N Eng J Med 1993; 329: 977-986.

8. Della Sala S, Bertoni G, Somazzi L et al. Impaired contrast sensitivity in diabetic patients with and without retinopathy: a new technique for rapid assessment. Br J Ophthalmol 1985; 69: 136-142.

9. Grant MB, Afzal A, Spoerri P et al. The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Investig Drugs 2004; 13: 1275-1293.

10. Grant MB, Caballero S Jr The potential role of octreotide in the treatment of diabetic retinopathy. Treat Endocrinol 2005; 4: 199-203.

11. Hammes HP Pathophysiological mechanisms of diabetic angiopathy. J Diabetes Complications 2003; 17 (2 Suppl): 16-19.

12. Hammes HP Pericytes and the pathogenesis of diabetic retinopathy. Horm Metab Res 2005; 37 (Suppl 1): 39-43.

13. Harada C, Mitamura Y, Harada T The role of cytokines and trophic factors in epiretinal membranes: involvement of signal transduction in glial cells. Prog Retin Eye Res 2006; 25: 149-164.

14. Chaturvedi N, Sjolie AK, Stephenson JM et al. Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. Lancet 1998; 351: 28-31.

15. Chiarelli F, Giannini C, Di Marzio D et al. Treating diabetic retinopathy by tackling growth factor pathways. Curr Opin Investig Drugs 2005; 6: 395-409.

16. Isomaa B, Henricsson M, Almgren P et al. The metabolic syndrome influences the risk of chronic complications in patients with type II diabetes. Diabetologia 2001; 44: 1148-1154.

17. Joy SV, Scates AC, Bearelly S et al. Ruboxistaurin, a protein kinase C beta inhibitor, as an emerging treatment for diabetes microvascular complications. Ann Pharmacother 2005; 39: 1693-1699.

18. Kalvodová B, Sosna T, Řehák J et al. Standardy pro diagnostiku a léčbu diabetické retinopatie a jejích komplikací. Doporučení České diabetologické společnosti a České oftalmologické společnosti. Vnitř Lék 2003; 49: 314-318.

19. Keech A, Simes RJ, Barter P et al. FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005; 366: 1849-1861.

20. Kim YH, Hong MK, Song JM et al. Diabetic retinopathy as a predictor of late clinical events following percutaneous coronary intervention. J Invasive Cardiol 2002; 14: 599-602.

21. Klein BE, Moss SE, Klein R et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudate. Ophthalmology 1991; 98: 1261-1265.

22. Klein R, Sharrett AR, Klein BE et al. ARIC Group. The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes: the atherosclerosis risk in communities study. Ophthalmology 2002; 109: 1225-1234.

23. Leal EC, Santiago AR, Ambrosio AF Old and new drug targets in diabetic retinopathy: from biochemical changes to inflammation and neurodegeneration. Curr Drug Targets CNS Neurol Disord 2005; 4: 421-434.

24. Leiden HA, Dekker JM, Moll AC et al. Blood pressure, lipids, and obesity are associated with retinopathy. Diabetes Care 2002; 25: 1320-1325.

25. Li Q, Puro DG Diabetes-induced dysfunction of the glutamate transporter in retinal Muller cells. Invest Ophthalmol Vis Sci 2002; 43: 3109-3116.

26. Lorenzi M, Gerhardinger C Early cellular and molecular changes induced by diabetes in the retina. Diabetologia 2001; 44: 791-804.

27. Maneschi F, Mashiter K, Kohner EM Insulin resistance and insulin deficiency in diabetic retinopathy of non-insulin-dependent diabetes. Diabetes 1983; 32: 82-87.

28. Murata T, Hata Y, Ishibashi T et al. Response of experimental retinal neovascularization to thiazolidinediones. Arch Ophthalmol 2001; 119: 709-717.

29. Orchard TJ, Forrest KY, Kuller LH et al. Pittsburgh Epidemiology of Diabetes Complications Study. Lipid and blood pressure treatment goals for type 1 diabetes: 10-year incidence data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care 2001; 24: 1053-1059.

30. Pelikánová T, Šimková R, Tesař V et al. Effect of acute hyperglycaemia on selected plasma and urinary cytokine antagonists in Type 1 diabetes mellitus. Diabetologia 2003; 46: 470-474.

31. Podesta F, Romeo G, Liu WH et al. Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro. Am J Pathol 2000; 156: 1025-1032.

32. Porta M, Allione A Current approaches and perspectives in the medical treatment of diabetic retinopathy. Pharmacol Ther 2004; 103: 167-177.

33. Porta M, Bandello F Diabetic retinopathy. A clinical update. Diabetologia 2002; 45: 1617-1634.

34. Porta M, Sjoelie AK, Chaturvedi N et al. EURODIAB Prospective Complications Study Group. Risk factors for progression to proliferative diabetic retinopathy in the EURODIAB Prospective Complications Study. Diabetologia 2001; 44: 2203-2209.

35. Rogers MS, D'Amato RJ The effect of genetic diversity on angiogenesis. Exp Cell Res 2006; 312: 561-574.

36. Singleton JR, Smith AG, Russell JW et al. Microvascular complications of impaired glucose tolerance. Diabetes 2003; 52: 2867-2873.

37. Sjolie AK, Moller F Medical management of diabetic retinopathy. Diabet Med 2004; 21: 666-672.

38. Škrha J. Patogeneze vaskulárních komplikací diabetu. In: Praktická diabetologie. Bartoš V, Pelikánová T (Eds). 3. vydání, Praha: Maxdorf 2003: 211-218.

39. Terasaki H, Hirose H, Miyake Y S-cone pathway sensitivity in diabetes measured with threshold versus intensity curves on flashed backgrounds. Invest Ophthalmol Vis Sci 1996; 37: 680-684.

40. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853.

41. UK Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703-713.

42. Van Wijngaarden P, Coster DJ, Williams KA Inhibitors of ocular neovascularization: promises and potential problems. JAMA 2005; 293: 1509-1513.

43. Wilkinson-Berka JL Angiotensin and diabetic retinopathy. Int J Biochem Cell Biol 2006; 38: 752-765.