#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Pathophysiology of diabetic retinopathy


Authors: T. Sosna
Authors‘ workplace: Primář: MUDr. Karel Sedláček ;  Oční oddělení Fakultní Thomayerovy nemocnice, Praha
Published in: Prakt. Lék. 2009; 89(2): 89-92
Category: Of different specialties

Overview

The basic pathogenic mechanism of diabetic retinopathy is hyperglycaemia. Capillary damage can be explained by several mechanisms: sorbitol overload, excessive storage of advanced glycosylation endproducts, oxidative stress or also cell apoptosis after paradoxical glucose starvation. In this article, the mechanism of capillary damage of the retina on the basis of haemorheological, hemodynamic and histopathologic changes is further analyzed. The specific influence of the retinal pigment epithelium is emphasized. Histopathological changes lead to basic microcirculatory anomalies caused by pericyte apoptotic cell death, damage of endothelial cells and the basal membrane. These changes lead to capillary dilatation, vascular occlusion and proliferation of new vessels, which is the main reason for further development of diabetic retinopathy.

Key words:
pathophysiology, diabetic retinopathy, hyperglycaemia, pericytes, endothelial cells.


Sources

1. Adamis, A.P, Miller, J.W., Bernal, M.T. et al. Elevated vascular permeability factor, vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am. J. Ophthalmol. 1994, 118, p. 445-450.

2. Ashton, N.A. Vascular basement membrane changes in diabetic retinopathy. Br. J. Ophthalmol. 1974, 58, p. 344-366.

3. Barnes, A.J., Kohner, E.M., Johnston, D.G., Alberti, K.G. Severe retinopathy and mild carbohydrate intolerance: possible role of insulin deficiency and elevated circulating growth hormone. Lancet 1985, 1(8444), p. 1465-1468.

4. Cagliero, E. Characteristics and mechanisms of high – glucose inducted overexpression of basement membrane components in cultured human endothelial cells. Diabetes 1991, 40, p. 102-109.

5. Cohen, R.A., Hennekens, C.H., Christen, W.G. et al. Determinants of retinopathy progression in type 1 diabetes mellitus. Am. J. Med. 1999, 107, p. 145-151.

6. Collier, A., Tymkewycz, P., Armstrong, R. et al. Increased platelet thromboxane receptors sensitivity in diabetic patients with proliferative retinopathy. Diabetologia 1986, 29, p. 471-474.

7. D’Amore, P. Mechanisms of retinal and chorioidal neovascularisation. Invest. Ophthalmol. Vis. Sci. 1994, 35, p. 3974-3979.

8. Danias, J., Stilianopoulou, F. Expression of IGE-l and IGF-2 genes in the adult rat eye. Curr. Eye Res. 1990, 9, p. 379-386.

9. Dorovini-Zis, K., Bowman, P.D., Betz, A.L., Goldstein, G.W. Hyperosmotic arabinose solutions open the tight junctions between brain capillary endothelial cells in cell culture. Brain Res. 1984, 302, p. 383-386.

10. Engerman, R.L., Kern, T.S. Aldoso reductase inhibitors fail to prevent retinopathy in diabetic and galactosaemic dogs. Diabetes 1993, 42, p. 820-825.

11. Faumenhaft, R., Abe, M., Mignatti, P., Rifkin, D.B. Basic fibroblast growth factor-induced activation of latent transforming growth factor - beta in endothelial cells: regulation of plasminogen activator activity. J. Cell Biol. 1992, 118, p. 901-909.

12. Forrester, J.V., Shafiee, A.F., Schroder, S. et al. The role of growth factors in proliferative diabetic retinopathy. Eye 1993, 7, p. 276-287.

13. Frank, R.N. The aldose reductase controversy. Diabetes 1994, 43, p. 169-172.

14. Glaser, B.M., Campochiaro, P.A., Davis, J.L., Jerdan, J.A. Retinal pigment epithelial cells release inhibitors of neovascularization. Ophthalmology 1987, 94, p. 780-784.

15. Gould, G., Bell, G.I. Facilitative glucose transporters: an expanding family. TIBS 1990, 15, p. 18-23.

16. Group, S.T.R. A randomised trial of sorbinil an aldoso reductase inhibitor, in diabetic retinopathy. Arch. Ophthalmol. 1990, 108, p. 1234-1244.

17. Harik, S.I., Kalaria, R.N., Whitney, P.M. Glucoso transporter are abundant in cells with occluding junction at blood retinal barrier. Proc. Natl. Acad. Sci. 1990, 87, p. 4261-4264.

18. Chantelau, E. Evidence that upregulation of serum IGF - 1 concentration can trigger acceleration of diabetic retinopathy. Br. J. Ophthalmol.1996, 82, p. 725-730.

19. Jaffe, A. Cell biology of endothelial cells. Human. Pathol. 1987, 18, p. 234-239.

20. Kubes, P., Granger, D.N. Nitric oxide modulates microvascular permeability. Am. J. Physiol. 1992, 262, p. 611-615.

21. Kwamura, M., Heineke, J.W., Chait, A. Pathophysiological concentrations of glucose promote oxidative modification of LDL by a superoxide dependent pathway. J. Clin. Invest. 1994, 94, p. 771-778.

22. Larson, H.W., Poulsen, J.E. Intra-ocular tension and blood sugar fluctuations in diabetes. Acta Ophtalmol. 1962, 40, p. 580-589.

23. Lee, T.S., Saltsman, K.A., Ohashi, H., King, G.L. Activation of protein kinase C by elevation of glucose concentration. Proc. Natl. Acad. Sci. 1990, 86, p. 5141-5145.

24. Li, W., Liu, X., Yanoff, M., Cohen, S., Ye, X. Cultured retinal capillary pericytes die by apoptosis after an abrupt fluctuation from high to low levels: a comparative study with retinal capillary endothelial cells. Diabetologia 1996, 39, p. 537-557.

25. Lyons, T.J., Li, W., Wells-Knect, M.C., Jokl, R. Toxicity of mildly modified LDL to cultured retinal capillary endothelial cells and pericytes. Diabetes 1994, 43, p. 1090-1095.

26. Moriarty, P., Bouton, M., Dickson, A., McLeod. D. Production of IGF-1 and IGF binding proteins by retinal cells in vitro. Br. J. Ophtalmol. 1994, 78, p. 638-642.

27. Poulsen, J.E. Recovery from retinopathy in the case of diabetes in Simmod‘s disease. Diabetes 1953, 2, p. 7-12.

28. Saudek, F., Bartoš, V., Vaněk, I. et al. Dlouhodobá léčba diabetu transplantací pankreatu. Čas. Lék. čes. 1996, 135, s. 348-653.

29. Schwieki, D., Itin, A., Soffer, D., Kesht, E. Vascular endothelial cell growth factor may mediate hypoxia – initiated angiogenesis. Nature 1992, 359, p. 843-845.

30. Sönksen, P.H., Russell-Jones, D., Jones, R.H. Growth hormone and diabetes mellitus. A review of sixty - three years of medicinal research and a glimpse into the future? Horm. Res. 1993, 40, p. 68-79.

31. Tarboletti, G., Roberts, D., Liotta, L., Giavezzi, R. Platelet thrombostatin modulates endothelial cell adhesion motility and growth: a potential angiogenesis regulatory factor. J. Cell. Biol. 1990, 111, p. 765-772.

32. Tooke, J.E. Microvascular haemodynamics in diabetics. Eye 1993, 7, p. 227-229.

33. Vondrová, H., Bartoš, V., Bouček, P. a kol. Vztah diabetické polyneuropatie k cévním a orgánovým komplikacím u diabetu mellitu I. typu. Čas. Lék. čes. 1990, 129, s. 1161-1165.

34. Watanabe, J., Wohtmann, H.J., Klein, R.L. et al. Enhancement of platelet aggregation by low density lipoprotein in patients with diabetes mellitus. Diabetes 1988, 37, p. 1652-1657.

35. Wilson, D.K., Bohren, K.M., Gababy, K.H., Quicho, F.A. An unlikely sugar substrate site in the 1.65 A Structure of the human aldoso reductase holoenzyme implicated in diabetic complications. Science 1992, 257, p. 81-84.

36. Wright, A., Kohner, E.M., Oakley, N.W. et al. Serum growth hormone levels and the response of diabetic retinopathy to pituitary ablation. BMJ 1969, 2(5653), p. 346–348.

37. Xia, P., Aiello, L.P., Ishii, H. et al. Characterisation of vascular endothelial growth factors effect of the activation of protein kinase C, its isoforms and endothelial cell growth. J. Clin. Invest. 1996, 98, p. 2018-2026.

38. Yasuda, Y., Clermont, A., Takahara, N. et al. Characterization of retinal abnormalities in vascular targeted overexpression of PKC beta2 isoform transgenic mice. Program and abstracts of the 63rd Scientific Sessions of the American Diabetes Association; June 13-17, 2003; New Orleans, Louisiana. Abstract 879-P.

Labels
General practitioner for children and adolescents General practitioner for adults
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#