Sulodexide – a new model for treating the early stages of diabetic retinopathy Review article
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Published:
Dec 4, 2023
Keywords:
glycocalyx, hard exusdates, sulodexide, diabetic retinopathy, blood vessel protection
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Abstract
Glycocalyx is the surface layer of endothelial cells, it lines the blood vessels and provides a cellular barrier against damage. Sulodexide has a protective effect on the glycocalyx and allows it to be rebuilt, and has anti-inflammatory, antioxidant, anticoagulant, and lipid profile-enhancing properties. Diabetic retinopathy damages the glycocalyx and vascular endothelium in the retina. Sulodexide rebuilds the glycocalyx and increases the integrity of the blood-retinal barrier, thereby protecting the retinal vasculature retina from hyperglycemia-induced damage. Clinical studies have confirmed that in non-proliferative diabetic retinopathy, sulodexide improves visual acuity, reduces microaneurysms and hard exudates. Further in a study evaluating recurrent retinal vein thrombosis, sulodexide reduced the recurrence rate. Sulodexide is a safe and well-tolerated drug and may play an important role in the treatment of diabetic retinopathy, both in reducing symptoms and improving visual function.
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1.
Wylęgała A. Sulodexide – a new model for treating the early stages of diabetic retinopathy. Ophthatherapy [Internet]. 2023Dec.4 [cited 2024Nov.23];10(4):269-76. Available from: https://journalsmededu.pl/index.php/ophthatherapy/article/view/2906
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Conservative treatment
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Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
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10. Mensah SA, Harding IC, Zhang M et al. Metastatic cancer cell attachment to endothelium is promoted by endothelial glycocalyx sialic acid degradation. AIChE J. 2019; 65. http://doi.org/10.1002/aic.16634.
11.Jarząbek K, Gabryel B, Urbanek T. Sulodexide in the treatment of vascular disease: its therapeutic action on the endothelium. Phlebol Rev. 2016; 4: 51-9. http://doi.org/10.5114/pr.2016.67742.
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14. Hoppensteadt DA, Fareed J. Pharmacological profile of sulodexide. Int Angiol. 2014; 3: 229-35.
15. Barbanti M, Guizzardi S, Calanni F et al. Antithrombotic and thrombolytic activity of sulodexide in rats. Int J Clin Lab Res. 1992; 22: 179-84. http://doi.org/10.1007/BF02591420.
16. Raffetto JD, Calanni F, Mattana P et al. Sulodexide promotes arterial relaxation via endothelium-dependent nitric oxide-mediated pathway. Biochem Pharmacol. 2019; 166: 347-56. http://doi.org/10.1016/j.bcp.2019.04.021.
17. Olde Engberink RHG, Rorije NMG, Lambers Heerspink HJ et al. The blood pressure lowering potential of sulodexide – a systematic review and meta‐analysis. Br J Clin Pharmacol. 2015; 80: 1245-53. http://doi.org/10.1111/bcp.12722.
18. Cicco G, Stingi GD, Vicenti P et al. Hemorheology and tissue oxygenation in hypertensives with lipoidoproteinosis and peripheral occlusive arterial disease (POAD) treated with sulodexide and pravastatine and evaluated with laser assisted optical rotational red cell analyzer (LORCA) and trans. Minerva Cardioangiol. 1999; 47: 351-9.
19. Andreozzi GM, Bignamini AA, Davì G et al. Sulodexide for the Prevention of Recurrent Venous Thromboembolism. Circulation. 2015; 132: 1891-7. http://doi.org/10.1161/CIRCULATIONAHA.115.016930.
20. Charakterystyka produktu leczniczego Vessel Due F. ChPL Vessel Due F. 2014.
21. Pompilio G, Integlia D, Raffetto J et al. Comparative Efficacy and Safety of Sulodexide and Other Extended Anticoagulation Treatments for Prevention of Recurrent Venous Thromboembolism: A Bayesian Network Meta-analysis. TH Open. 2020; 04: e80-93. http://doi.org/10.1055/s-0040-1709731.
22. Bikdeli B, Chatterjee S, Kirtane AJ et al. Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials. Semin Thromb Hemost. 2020; 46: 908-18. http://doi.org/10.1055/s-0040-1716874.
23. Radhakrishnamurthy B, Sharma C, Bhandaru RR et al. Studies of chemical and biologic properties of a fraction of sulodexide, a heparin- like glycosaminoglycan. Atherosclerosis. 1986; 60: 141-9. http://doi.org/10.1016/0021-9150(86)90006-7.
24. Giurdanella G, Lazzara F, Caporarello N et al. Sulodexide prevents activation of the PLA2/COX-2/VEGF inflammatory pathway in human retinal endothelial cells by blocking the effect of AGE/RAGE. Biochem Pharmacol. 2017; 142: 145-54.
25. Jo H, Jung SH, Kang J et al. Sulodexide inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. BMB Rep. 2014; 47: 637-42. http://doi.org/10.5483/BMBRep.2014.47.11.009.
26. Gericke A, Suminska-Jasińska K, Bręborowicz A. Sulodexide reduces glucose induced senescence in human retinal endothelial cells. Sci Rep. 2021; 11: 11532. http://doi.org/10.1038/s41598-021-90987-w.
27. Orlenko VL, Tronko KM. Efficacy of using glucosamine (sulodexide) in the treatment of diabetic retinopathy in patients with type 2 diabetes mellitus (T2DM) with increased body mass. Sci Eur. 2016; 8: 41–6.
28. Belcaro G, Dugall M, Bradford HD et al. Recurrent retinal vein thrombosis: prevention with Aspirin, Pycnogenol®, ticlopidine, or sulodexide. Minerva Cardioangiol. 2019; 67. http://doi.org/10.23736/S0026-4725.19.04891-6.
29. Lamblova K, Mlcoch T, Mazalova M et al. Cost-Effectiveness Analysis of Sulodexide in Patients with Non-Proliferative Diabetic Retinopathy in the Czech Republic. Value Heal. 2016; 19: A568. http://doi.org/10.1016/j.jval.2016.09.1283.
2. Mazur R, Wylęgała A, Świerkosz W et al. Retinopatia cukrzycowa – najczęstsze powikłanie. Możliwości profilaktyki i leczenia. Diabetol po Dyplomie. 2018; 15: 25-31.
3. Wylęgała E, Wylęgała A. Retinopatia cukrzycowa – możliwości leczenia. Diabetol po Dyplomie. 2017; 14: 11-7.
4. Wylęgała E, Wylęgała A. Cukrzycowa choroba narządu wzroku. In: Leczenie powikłań cukrzycy i chorób z nią współistniejących. Franek E (red).Wydawnictwo San Roque, Warszawa 2018.
5. Pilśniak A, Wylęgała A, Otto-Buczkowska E. Ophthalmologic disorders in adolescents with type 1 diabetes. CD 2020; 9(6): 493-6.
6. Sędziak‐Marcinek B, Wylęgała A, Chełmecka E et al. How to achieve near‐normal visual acuity with bevacizumab in diabetic macular edema patients. J Clin Med. 2021; 10(16): 3572.
7. Wylęgała A, Wylęgała E. Powikłania okulistyczne u chorych na otyłość. In: Obesitologia kliniczna. Olszanecka-Glinianowicz M (red). α-medica press, Bielsko-Biała 2021: 477-82.
8. Dauth A, Bręborowicz A, Ruan Y et al. Sulodexide Prevents Hyperglycemia-Induced Endothelial Dysfunction and Oxidative Stress in Porcine Retinal Arterioles. Antioxidants. 2023; 12: 388. http://doi.org/10.3390/antiox12020388.
9. Broekhuizen LN, Lemkes BA, Mooij HL et al. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia. 2010; 53: 2646–55. http://doi.org/10.1007/s00125-010-1910-x.
10. Mensah SA, Harding IC, Zhang M et al. Metastatic cancer cell attachment to endothelium is promoted by endothelial glycocalyx sialic acid degradation. AIChE J. 2019; 65. http://doi.org/10.1002/aic.16634.
11.Jarząbek K, Gabryel B, Urbanek T. Sulodexide in the treatment of vascular disease: its therapeutic action on the endothelium. Phlebol Rev. 2016; 4: 51-9. http://doi.org/10.5114/pr.2016.67742.
12.Foote CA, Soares RN, Ramirez‐Perez FI et al. Endothelial Glycocalyx. In: Comprehensive Physiology. Wiley; 2022: 3781–811. http://doi.org/10.1002/cphy.c210029.
13. Harenberg J. Review of pharmacodynamics, pharmacokinetics, and therapeutic properites of sulodexide. Med Res Rev. 1998; 18: 1-20. http://doi.org/10.1002/(SICI)1098-1128(199801)18:1<1::AID-MED1>3.0.CO;2-4.
14. Hoppensteadt DA, Fareed J. Pharmacological profile of sulodexide. Int Angiol. 2014; 3: 229-35.
15. Barbanti M, Guizzardi S, Calanni F et al. Antithrombotic and thrombolytic activity of sulodexide in rats. Int J Clin Lab Res. 1992; 22: 179-84. http://doi.org/10.1007/BF02591420.
16. Raffetto JD, Calanni F, Mattana P et al. Sulodexide promotes arterial relaxation via endothelium-dependent nitric oxide-mediated pathway. Biochem Pharmacol. 2019; 166: 347-56. http://doi.org/10.1016/j.bcp.2019.04.021.
17. Olde Engberink RHG, Rorije NMG, Lambers Heerspink HJ et al. The blood pressure lowering potential of sulodexide – a systematic review and meta‐analysis. Br J Clin Pharmacol. 2015; 80: 1245-53. http://doi.org/10.1111/bcp.12722.
18. Cicco G, Stingi GD, Vicenti P et al. Hemorheology and tissue oxygenation in hypertensives with lipoidoproteinosis and peripheral occlusive arterial disease (POAD) treated with sulodexide and pravastatine and evaluated with laser assisted optical rotational red cell analyzer (LORCA) and trans. Minerva Cardioangiol. 1999; 47: 351-9.
19. Andreozzi GM, Bignamini AA, Davì G et al. Sulodexide for the Prevention of Recurrent Venous Thromboembolism. Circulation. 2015; 132: 1891-7. http://doi.org/10.1161/CIRCULATIONAHA.115.016930.
20. Charakterystyka produktu leczniczego Vessel Due F. ChPL Vessel Due F. 2014.
21. Pompilio G, Integlia D, Raffetto J et al. Comparative Efficacy and Safety of Sulodexide and Other Extended Anticoagulation Treatments for Prevention of Recurrent Venous Thromboembolism: A Bayesian Network Meta-analysis. TH Open. 2020; 04: e80-93. http://doi.org/10.1055/s-0040-1709731.
22. Bikdeli B, Chatterjee S, Kirtane AJ et al. Sulodexide versus Control and the Risk of Thrombotic and Hemorrhagic Events: Meta-Analysis of Randomized Trials. Semin Thromb Hemost. 2020; 46: 908-18. http://doi.org/10.1055/s-0040-1716874.
23. Radhakrishnamurthy B, Sharma C, Bhandaru RR et al. Studies of chemical and biologic properties of a fraction of sulodexide, a heparin- like glycosaminoglycan. Atherosclerosis. 1986; 60: 141-9. http://doi.org/10.1016/0021-9150(86)90006-7.
24. Giurdanella G, Lazzara F, Caporarello N et al. Sulodexide prevents activation of the PLA2/COX-2/VEGF inflammatory pathway in human retinal endothelial cells by blocking the effect of AGE/RAGE. Biochem Pharmacol. 2017; 142: 145-54.
25. Jo H, Jung SH, Kang J et al. Sulodexide inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy. BMB Rep. 2014; 47: 637-42. http://doi.org/10.5483/BMBRep.2014.47.11.009.
26. Gericke A, Suminska-Jasińska K, Bręborowicz A. Sulodexide reduces glucose induced senescence in human retinal endothelial cells. Sci Rep. 2021; 11: 11532. http://doi.org/10.1038/s41598-021-90987-w.
27. Orlenko VL, Tronko KM. Efficacy of using glucosamine (sulodexide) in the treatment of diabetic retinopathy in patients with type 2 diabetes mellitus (T2DM) with increased body mass. Sci Eur. 2016; 8: 41–6.
28. Belcaro G, Dugall M, Bradford HD et al. Recurrent retinal vein thrombosis: prevention with Aspirin, Pycnogenol®, ticlopidine, or sulodexide. Minerva Cardioangiol. 2019; 67. http://doi.org/10.23736/S0026-4725.19.04891-6.
29. Lamblova K, Mlcoch T, Mazalova M et al. Cost-Effectiveness Analysis of Sulodexide in Patients with Non-Proliferative Diabetic Retinopathy in the Czech Republic. Value Heal. 2016; 19: A568. http://doi.org/10.1016/j.jval.2016.09.1283.