Calcium dobesilate in the treatment of diabetic retinopathy.
ABSTRACT The incidence of diabetic retinopathy is still increasing in developed countries. Tight glycemic control and laser therapy reduce vision loss and blindness, but do not reverse existing ocular damage and only slow the progression of the disease. New pharmacologic agents that are currently under development and are specifically directed against clearly defined biochemical targets (i.e. aldose reductase inhibitors and protein kinase C-beta inhibitors) have failed to demonstrate significant efficacy in the treatment of diabetic retinopathy in clinical trials. In contrast, calcium dobesilate (2,5-dihydroxybenzenesulfonate), which was discovered more than 40 years ago and is registered for the treatment of diabetic retinopathy in more than 20 countries remains, to our knowledge, the only angioprotective agent that reduces the progression of this disease. An overall review of published studies involving calcium dobesilate (CLS 2210) depicts a rather 'non-specific' compound acting moderately, but significantly, on the various and complex disorders that contribute to diabetic retinopathy. Recent studies have shown that calcium dobesilate is a potent antioxidant, particularly against the highly damaging hydroxyl radical. In addition, it improves diabetic endothelial dysfunction, reduces apoptosis, and slows vascular cell proliferation.
SourceAvailable from: Mohammadreza Abbaspour[Show abstract] [Hide abstract]
ABSTRACT: Purpose: To evaluate the effect of oral calcium dobesilate (Doxium) on macular thickness in clinically significant macular edema (CSME) Methods: Overall, 71 eyes of 40 patients with non-proliferative diabetic retinopathy and clinically significant macular edema were included. All patients were received laser treatment for macular edema. Coherence optical tomography was used to determine the retinal thickness. Patients were randomized into two groups: group A received three Doxium capsule daily and group B received three placebo capsule daily for six months. Results: The mean macular thickness before and after treatment in the group A was 340 and 257 micrometers respectively (24.5% reduced), and in the group B was 336 micrometers and 263 micrometers respectively (21.5% reduced). Macular thickness significantly decreased after treatment in both groups and the reduction in group A is higher but the difference of reduction between the two groups was not statistically significant (P>0.05). Conclusion: In respect to the effect of adding oral Doxium to Laser Photocoagulation on the macular thickness in patients with diabetic macular edema, this study showed no statistically significant difference between Doxium and placebo.
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ABSTRACT: AIMS/HYPOTHESIS: The realisation that targeting agents in the vitreous is an effective approach to treating patients with diabetic retinopathy (DR) has increased awareness that changes in the composition/bioactivity of the vitreous is a contributor to the pathogenesis of DR. The overall goal of this study was to test the hypothesis that the vitreous has regression activity, and that lysophosphatidic acid (LPA) contributes to such activity. LPA is a bioactive phospholipid present in many biological fluids, and has been recently appreciated for its ability to promote regression of blood vessels. METHODS: Vitreous-mediated regression was monitored on tubes organised from primary retinal endothelial cells or neovessels that sprouted from retinal explants. LPA was quantified radioenzymatically. RESULTS: Bovine and human vitreous promoted regression of retinal explant vessels and of tubes organised from primary retinal endothelial cells. LPA was a substantial component of this regression activity. Comparing the regression activities of vitreous from patients with different stages of DR revealed that, as patients developed proliferative diabetic retinopathy (PDR), vitreous lost its ability to promote regression, even though the amount of LPA did not change. The underlying mechanism was a PDR-vitreous-mediated insensitivity to LPA, which could be overcome pharmacologically. CONCLUSIONS/INTERPRETATION: Our findings suggest that a decline in the responsiveness to regression factors such as LPA, which are naturally present in the vitreous, contributes to the pathogenesis of PDR.Diabetologia 03/2013; 56(6). DOI:10.1007/s00125-013-2884-2 · 6.88 Impact Factor
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ABSTRACT: Diabetic retinopathy (DR) is a hyperglycemia-induced ischemic disorder characterized by microvascular dysfunction and neovascularization. It is a leading cause of blindness in many countries, yet efficient drugs are limited now for prevention and treatment of DR. Low molecular weight fucoidan (LMWF), extract from brown algae, has been shown to possess multiple biological activities like anti-inflammation, anti-oxidation and anti-aggregation, which all could be beneficial for attenuating ischemia-induced tissue damages. Here, by comparing with calcium dobesilate, the potent antioxidant compound currently used for the treatment of DR, we investigated the protective effect of LMWF against DR in streptozotocin-induced diabetic mice and high glucose-promoted vascular endothelial growth factor (VEGF) production and cell proliferation in microvascular endothelial cells. One week after diabetes induction, the mice were administered with LMWF (50, 100 or 200 mg/kg/day) or calcium dobesilate (200 mg/kg/day) for four months, then the retinal pathological changes and neovascularization were detected by hematoxylin-eosin staining and fluorescein dextran angiography, respectively. Immunofluorescence staining, ELISA and RT-PCR were used to examine the expression levels of hypoxia-inducible factor-1α (HIF-1α) and VEGF in retina and endothelial cells. Here, we found that LMWF resembled calcium dobesilate, in alleviating retinal pathological change and hindering neovascularization due to diabetes in vivo. The relative levels of VEGF expression and HIF-1α induction were also less in retinas of LMWF- or calcium dobesilate-treated diabetic mice than those in retinas of control mice. Furthermore, high glucose-induced VEGF overexpression and cell proliferation in primary cultured vascular endothelial cells were also inhibited by LMWF in a dose-dependent manner. Therefore, this study demonstrated that LMWF alleviates diabetic retinal neovascularization and damage likely through lowering HIF-1α and VEGF expressions, providing a potential candidate drug for prevention and treatment of diabetic retinopathy.Experimental Eye Research 06/2013; 115. DOI:10.1016/j.exer.2013.06.011 · 3.02 Impact Factor