Calcium Dobesilate in the Treatment of Diabetic Retinopathy

ArticleinTreatments in Endocrinology 4(4):221-32 · February 2005with74 Reads
DOI: 10.2165/00024677-200504040-00003 · Source: PubMed
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.

    • "Calcium dobesilate was chosen to be the control agent. The efficacy and safety of calcium dobesilate as a vasoprotective agent have been confirmed in many randomized clinical controlled trials because of its antioxidant and antiapoptotic properties, which can improve diabetic endothelial dysfunction and slow vascular cell proliferation [12] to effectively treat DR at the systematic and local ocular levels [13] "
    [Show abstract] [Hide abstract] ABSTRACT: This randomized, double-dummy, double-blind study was to observe the therapeutic effects of compound Danshen dripping pill (CDDP) in treating early diabetic retinopathy (DR). All the 57 type 2 diabetes cases in nonproliferative diabetic retinopathy (NPDR) stage were divided into two groups randomly: 28 cases treated with CDDP as the treated group and 29 cases treated with calcium dobesilate as the control group. The best corrected visual acuity (BCVA) in the treated group was significantly improved after treatment when compared to that before treatment ( P < 0.05 ). Mean defect (MD) of visual field, hemorrhage area of the fundus, microaneurysm number, fluorescent leakage area, and capillary nonperfusion area evaluated by visual field, fundus photography, and fundus fluorescein angiography in the treated group had the same results as BCVA. However, there was no statistical difference in each index between the two groups. No obvious adverse events with clinical significance occurred. Our present study showed that CDDP has a similar improvement and safety to calcium dobesilate for NPDR. In future DR treatments, CDDP may function as the auxiliary drug.
    Full-text · Article · Oct 2015 · Evidence-based Complementary and Alternative Medicine
    Dan Luo Dan Luo Yali Qin Yali Qin Wei Yuan Wei Yuan +2 more authors... Hui Deng Hui Deng
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    • "Despite promising results from animal models of diabetic retinopathy , due to lack of well-designed longitudinal cohort studies and clinical trials, results from diabetic patients have been inconclusive . Calcium dobesilate (2, 5-dihydroxybenzenesulfonate, a compound with potent antioxidant capacity against hydroxyl radical), and pycnogenol (with both free radical scavenging and anti-inflammatory properties) reduces the progression of diabetic retinopathy (Garay et al., 2005; Spadea and Balestrazzi, 2001). In a small clinical trial, oral administration of a-lipoic acid with genistein and vitamins for 30 days in patients with proliferative diabetic retinopathy, has shown beneficial effects on ERG oscillatory potential (Nebbioso et al., 2012). "
    [Show abstract] [Hide abstract] ABSTRACT: Diabetic retinopathy remains the major cause of blindness among working age adults. Although a number of metabolic abnormalities have been associated with its development, due to complex nature of this multi-factorial disease, a link between any specific abnormality and diabetic retinopathy remains largely speculative. Diabetes increases oxidative stress in the retina and its capillary cells, and overwhelming evidence suggests a bidirectional relationship between oxidative stress and other major metabolic abnormalities implicated in the development of diabetic retinopathy. Due to increased production of cytosolic reactive oxygen species, mitochondrial membranes are damaged and their membrane potentials are impaired, and complex III of the electron transport system is compromised. Suboptimal enzymatic and nonenzymatic antioxidant defense system further aids in the accumulation of free radicals. As the duration of the disease progresses, mitochondrial DNA (mtDNA) is damaged and the DNA repair system is compromised, and due to impaired transcription of mtDNA-encoded proteins, the integrity of the electron transport system is encumbered. Due to decreased mtDNA biogenesis and impaired transcription, superoxide accumulation is further increased, and the vicious cycle of free radicals continues to self-propagate. Diabetic milieu also alters enzymes responsible for DNA and histone modifications, and various genes important for mitochondrial homeostasis, including mitochondrial biosynthesis, damage and antioxidant defense, undergo epigenetic modifications. Although antioxidant administration in animal models has yielded encouraging results in preventing diabetic retinopathy, controlled longitudinal human studies remain to be conducted. Furthermore, the role of epigenetic in mitochondrial homeostasis suggests that regulation of such modifications also has potential to inhibit/retard the development of diabetic retinopathy. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · May 2015 · Progress in Retinal and Eye Research
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    • "Despite these findings, the results of clinical trials of antioxidant therapy are contradictory. Studies with limited numbers of patients suggest that antioxidant therapy with dobesilate and pycnogenol delay DR progression394041. In contrast, others have found no association between antioxidant therapy and decreased progression of DR [42, 43]. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Mar 2013 · Diabetologia
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