Advertisement

Der Diabetologe

, Volume 14, Issue 8, pp 542–549 | Cite as

Pathomechanismen der diabetischen Retinopathie

  • Hansjürgen Agostini
  • Gottfried Martin
  • Focke Ziemssen
Leitthema
  • 31 Downloads

Zusammenfassung

Die Entstehung der diabetischen Retinopathie hängt eng mit der Störung der inneren Blut-Retina-Schranke zusammen. Gleichzeitig werden Schädigungsmechanismen der Neurodegeneration beobachtet, die über Gliazellen vermittelt und bei bisherigen Einteilungen der diabetischen Retinopathie nur unzureichend berücksichtigt werden. Bezüglich der Pathophysiologie der diabetischen Retinopathie wurden inzwischen viele Erkenntnisse, v. a. aus Tiermodellen, histologischen Studien oder Messungen von Zytokinen im Kammerwasser und im Glaskörper von Menschen mit Diabetes, gewonnen. Therapeutische Konsequenzen haben sich aber bisher insbesondere aus dem Wissen über die Pathogenese der mikrovaskulären Veränderungen abgeleitet, indem der permeabilitätssteigernde „vascular endothelial growth factor“ gehemmt wird oder entzündungshemmende Steroide genutzt werden.

Schlüsselwörter

Blut-Retina-Schranke Neurodegeneration Hypoxie Neovaskularisation, pathologisch „Advanced glycation endproducts“ 

Pathomechanisms of diabetic retinopathy

Abstract

The pathogenesis of diabetic retinopathy (DR) is closely linked to disruption of the inner blood-retinal barrier; however, there is also an ongoing process of inflammation-driven neurodegeneration from the beginning, triggered by glial cell activity but insufficiently taken into consideration for previous classifications of DR. With respect to the pathophysiology of DR, profound knowledge has been gained from animal models, histopathological studies of human tissue and the biochemical analysis of cytokines in samples from the anterior chamber and vitreous body; however, so far only insights into the microvascular changes and mainly those driven by angiogenic factors, such as vascular endothelial growth factor (VEGF), are reflected in therapeutic approaches as are the pleiotropic actions triggered by local steroids.

Keywords

Blood-retinal barrier Neurodegeneration Hypoxia Neovascularization, pathologic Advanced glycation endproducts 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

H. Agostini, G. Martin und F. Ziemssen geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Boss JD, Singh PK, Pandya HK et al (2017) Assessment of neurotrophins and inflammatory mediators in vitreous of patients with diabetic retinopathy. Invest Ophthalmol Vis Sci 58:5594–5603.  https://doi.org/10.1167/iovs.17-21973 CrossRefGoogle Scholar
  2. 2.
    Chang Y‑C, Wu W‑C (2013) Dyslipidemia and diabetic retinopathy. Rev Diabet Stud 10:121–132.  https://doi.org/10.1900/RDS.2013.10.121 CrossRefGoogle Scholar
  3. 3.
    Daruich A, Matet A, Moulin A et al (2018) Mechanisms of macular edema: beyond the surface. Prog Retin Eye Res 63:20–68.  https://doi.org/10.1016/j.preteyeres.2017.10.006 CrossRefGoogle Scholar
  4. 4.
    Davis MD, Sheetz MJ, Aiello LP et al (2009) Effect of ruboxistaurin on the visual acuity decline associated with long-standing diabetic macular edema. Invest Ophthalmol Vis Sci 50:1–4.  https://doi.org/10.1167/iovs.08-2473 CrossRefGoogle Scholar
  5. 5.
    Friedrichs P, Schlotterer A, Sticht C et al (2017) Hyperglycaemic memory affects the neurovascular unit of the retina in a diabetic mouse model. Diabetologia 60:1354–1358.  https://doi.org/10.1007/s00125-017-4254-y CrossRefGoogle Scholar
  6. 6.
    Gardner TW, Abcouwer SF, Barber AJ, Jackson GR (2011) An integrated approach to diabetic retinopathy research. Arch Ophthalmol 129:230–235.  https://doi.org/10.1001/archophthalmol.2010.362 CrossRefGoogle Scholar
  7. 7.
    Gella L, Raman R, Kulothungan V et al (2015) Impairment of colour vision in diabetes with no retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular Genetics Study (SNDREAMS- II, report 3). PLoS ONE 10:e129391.  https://doi.org/10.1371/journal.pone.0129391 CrossRefGoogle Scholar
  8. 8.
    Hammes H‑P (2005) Pericytes and the pathogenesis of diabetic retinopathy. Horm Metab Res 37(Suppl 1):39–43.  https://doi.org/10.1055/s-2005-861361 CrossRefGoogle Scholar
  9. 9.
    Hammes H‑P (2018) Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond. Diabetologia 61:29–38.  https://doi.org/10.1007/s00125-017-4435-8 CrossRefGoogle Scholar
  10. 10.
    Hammes H‑P (2018) Medikamentöse Therapie der diabetischen Retinopathie – Die diabetologische Perspektive. Diabetologe.  https://doi.org/10.1007/s11428-018-0372-5 CrossRefGoogle Scholar
  11. 11.
    Hosoya K, Tachikawa M (2012) The inner blood-retinal barrier: molecular structure and transport biology. Adv Exp Med Biol 763:85–104Google Scholar
  12. 12.
    Jiang M‑S, Yuan Y, Gu Z‑X, Zhuang S‑L (2016) Corneal confocal microscopy for assessment of diabetic peripheral neuropathy: a meta-analysis. Br J Ophthalmol 100:9–14.  https://doi.org/10.1136/bjophthalmol-2014-306038 CrossRefGoogle Scholar
  13. 13.
    Klein R, Klein BE, Moss SE, Cruickshanks KJ (1995) The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology 102:7–16CrossRefGoogle Scholar
  14. 14.
    Lakk M, Vazquez-Chona F, Yarishkin O, Križaj D (2018) Dyslipidemia modulates Müller glial sensing and transduction of ambient information. Neural Regen Res 13:207–210.  https://doi.org/10.4103/1673-5374.226383 CrossRefGoogle Scholar
  15. 15.
    Lange CAK, Stavrakas P, Luhmann UFO et al (2011) Intraocular oxygen distribution in advanced proliferative diabetic retinopathy. Am J Ophthalmol 152:406–412.e3.  https://doi.org/10.1016/j.ajo.2011.02.014 CrossRefGoogle Scholar
  16. 16.
    Milne R, Brownstein S (2013) Advanced glycation end products and diabetic retinopathy. Amino Acids 44:1397–1407.  https://doi.org/10.1007/s00726-011-1071-3 CrossRefGoogle Scholar
  17. 17.
    Moran EP, Wang Z, Chen J et al (2016) Neurovascular cross talk in diabetic retinopathy: pathophysiological roles and therapeutic implications. Am J Physiol Heart Circ Physiol 311:H738–H749.  https://doi.org/10.1152/ajpheart.00005.2016 CrossRefGoogle Scholar
  18. 18.
    Rabbani N, Thornalley PJ (2018) Glyoxalase 1 modulation in obesity and diabetes. Antioxid Redox Signal.  https://doi.org/10.1089/ars.2017.7424 CrossRefGoogle Scholar
  19. 19.
    Rask-Madsen C, King GL (2013) Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab 17:20–33.  https://doi.org/10.1016/j.cmet.2012.11.012 CrossRefGoogle Scholar
  20. 20.
    Reddy MA, Zhang E, Natarajan R (2015) Epigenetic mechanisms in diabetic complications and metabolic memory. Diabetologia 58:443–455.  https://doi.org/10.1007/s00125-014-3462-y CrossRefGoogle Scholar
  21. 21.
    Rübsam A, Parikh S, Fort PE (2018) Role of inflammation in diabetic retinopathy. Int J Mol Sci.  https://doi.org/10.3390/ijms19040942 CrossRefGoogle Scholar
  22. 22.
    Sacks FM, Hermans MP, Fioretto P et al (2014) Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries. Circulation 129:999–1008.  https://doi.org/10.1161/CIRCULATIONAHA.113.002529 CrossRefGoogle Scholar
  23. 23.
    Sato Y, Kamata A, Matsui M (1993) Clinical study of venous abnormalities in diabetic retinopathy. Jpn J Ophthalmol 37:136–142Google Scholar
  24. 24.
    Schorr SG, Hammes H‑P, Müller UA et al (2016) The prevention and treatment of retinal complications in diabetes. Dtsch Arztebl Int 113:816–823.  https://doi.org/10.3238/arztebl.2016.0816 CrossRefGoogle Scholar
  25. 25.
    Sousa Silva M, Gomes RA, Ferreira AEN et al (2013) The glyoxalase pathway: the first hundred years... and beyond. Biochem J 453:1–15.  https://doi.org/10.1042/BJ20121743 CrossRefGoogle Scholar
  26. 26.
    Verma A, Rani PK, Raman R et al (2009) Is neuronal dysfunction an early sign of diabetic retinopathy? Microperimetry and spectral domain optical coherence tomography (SD-OCT) study in individuals with diabetes, but no diabetic retinopathy. Eye (Lond) 23:1824–1830.  https://doi.org/10.1038/eye.2009.184 CrossRefGoogle Scholar
  27. 27.
    Vujosevic S, Micera A, Bini S et al (2015) Aqueous humor biomarkers of Müller cell activation in diabetic eyes. Invest Ophthalmol Vis Sci 56:3913–3918.  https://doi.org/10.1167/iovs.15-16554 CrossRefGoogle Scholar
  28. 28.
    Vujosevic S, Torresin T, Berton M et al (2017) Diabetic macular edema with and without subfoveal neuroretinal detachment: two different morphologic and functional entities. Am J Ophthalmol 181:149–155.  https://doi.org/10.1016/j.ajo.2017.06.026 CrossRefGoogle Scholar
  29. 29.
    Wu H, Hwang D‑K, Song X, Tao Y (2017) Association between aqueous cytokines and diabetic retinopathy stage. J Ophthalmol.  https://doi.org/10.1155/2017/9402198 CrossRefGoogle Scholar
  30. 30.
    Yan L‑J (2014) Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. J Diabetes Res.  https://doi.org/10.1155/2014/137919 CrossRefGoogle Scholar
  31. 31.
    Yozgatli K, Lefrandt JD, Noordzij MJ et al (2018) Accumulation of advanced glycation end products is associated with macrovascular events and glycaemic control with microvascular complications in type 2 diabetes mellitus. Diabet Med.  https://doi.org/10.1111/dme.13651 CrossRefGoogle Scholar
  32. 32.
    Yu C‑G, Yuan S‑S, Yang L‑Y et al (2018) Angiopoietin-like 3 is a potential biomarker for retinopathy in type 2 diabetic patients. Am J Ophthalmol.  https://doi.org/10.1016/j.ajo.2018.03.040 CrossRefGoogle Scholar
  33. 33.
    German Ophthalmological Society, Retina Society, Professional Association of German Ophthalmologists (2013) Treatment of diabetic maculopathy. Ophthalmologe 110:568–588.  https://doi.org/10.1007/s00347-013-2885-z CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • Hansjürgen Agostini
    • 1
  • Gottfried Martin
    • 1
  • Focke Ziemssen
    • 2
  1. 1.Klinik für Augenheilkunde, Medizinische FakultätUniversitätsklinikum FreiburgFreiburgDeutschland
  2. 2.Department für AugenheilkundeUniversität TübingenTübingenDeutschland

Personalised recommendations