sulindac and Diabetic-Retinopathy

To evaluate the effects of long-term treatment with sulindac on the progression of diabetic retinopathy (DR).. 40 Japanese patients with type 2 diabetes were enrolled in a randomized, single-blind controlled trial in which the effects of sulindac (200 mg/day, 100 mg twice a day; n = 16 patients) on the progression of DR were compared to controls (24 patients) for 3 years. All patients were comparable in their age, gender, duration of disease, body mass index, dipstick proteinuria, insulin therapy, glycemic control, and clinical stages of DR. Outcome was determined by comparing parameters of retinopathy in fundus photographs that were taken at time 0 to those taken 1, 2, and 3 years after the initiation of treatment.. Patients in the sulindac group did not develop DR during the course of treatment nor was there progression of pathology in those who began the study with mild non-proliferative DR (NPDR). On the other hand, six patients progressed to mild NPDR in the control group--three at year 1 and three at year 3--and an additional patient progressed to severe NPDR from mild NPDR by year 1 and to proliferative DR by year 2. The findings at year 3 in the sulindac group were significantly (p < 0.05) different from the control group. None of the patients experienced any adverse effects of treatment.. Long-term treatment with sulindac was clinically effective in decreasing the progression of mild DR in type 2 diabetic patients in this pilot study.

Topics: Aged; Cyclooxygenase Inhibitors; Diabetic Retinopathy; Disease Progression; Female; Humans; Male; Middle Aged; Single-Blind Method; Sulindac

To study the effect of sulindac on the alteration of the blood-retinal barrier, 24 insulin-dependent diabetic patients with minimal or no retinopathy were randomly assigned to receive either oral sulindac (200 mg twice daily) or a placebo for a period of six months. All patients underwent fundus photography, fluorescein angiography, and vitreous fluorophotometry before treatment and after 1, 3, and 6 months of treatment. Vitreous fluorophotometry data showed that there were fewer alterations of the blood-retinal barrier in the sulindac group compared with the placebo group during the six-month study period.

Topics: Administration, Oral; Cell Membrane Permeability; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Double-Blind Method; Fluorescein; Fluoresceins; Humans; Indenes; Retina; Rheology; Sulindac

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Basement Membrane; Capillaries; Diabetic Retinopathy; Dogs; Retinal Vessels; Sulindac; Tumor Necrosis Factor-alpha

Angiogenesis, the process of new blood vessel formation, is the key event in the mechanism of several pathological processes including diabetic retinopathy. The physiological control of angiogenesis depends on the balance between stimulatory and inhibitory factors. Therefore, a number of anti-angiogenic approaches has been developed, many of them based on the inhibition of the functional activity of pro-angiogenic factors. The aim of the present study was to compare the anti-angiogenic effectiveness of sulindac sulfone and some herbal compounds in the serum-induced angiogenesis test performed in Balb/c mice. Pooled sera from 35 patients with diabetes type 2 and retinopathy were used as pro-angiogenic stimuli. The strongest inhibitory effect was observed for the sulindac sulfone and ursolic acid in the highest concentration of 200 micro g/ml, as well as for the low-dosage concomitant treatment with 2 micro g/ml of epigallocatechin gallate (EGCG, green tea flavanol), ursolic acid (plant-derived triterpenoid), sulindac sulfone and convalamaroside (steroidal saponin). Combination treatment was significantly more effective than monotherapy with medium (20 micro g/ml) or lowest doses of tested compounds. The present study is the first to demonstrate the potent anti-angiogenic effect of the combination therapy comprising of plant-derived extracts and sulindac sulfone, as tested in the in vivo angiogenesis experimental model with sera of non-proliferative diabetic retinopathy patients used as the pro-angiogenic stimuli. We think that it might be the first step toward application of some of these compounds, in the future, in preventive anti-angiogenic therapy of these patients, as well, as in the treatment of later, proliferative stage of this disease.

Topics: Angiogenesis Inducing Agents; Animals; Cell Proliferation; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Male; Mice; Mice, Inbred BALB C; Neovascularization, Physiologic; Plants, Medicinal; Serum; Sulindac

To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology.. Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status.. Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p< or =0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p< or =0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal capillary basement membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p< or =0.0001).. This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Collagen; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Disease Models, Animal; Dogs; Glycation End Products, Advanced; Male; Microscopy, Electron; Reference Values; Retinal Vessels; Skin; Sulindac

Capillary basement membrane thickening is one of the earliest histologic lesions in diabetic retinopathy. Its pathogenesis is not understood; however, recent evidence suggests that aldose reductase may play a role. In this study, a new animal model, the diabetic cat, was used to determine whether retinal capillary basement membrane thickening occurred early in the course of hyperglycemia, and if so, whether it could be inhibited by sulindac, an aldose reductase inhibitor. Retinal capillary basement membrane thickness was significantly increased in diabetic cats compared to normal cats (114 +/- 15 vs 72 +/- 12 nm, mean +/- SD) [corrected]. Basement membrane thickness was significantly less in sulindac-treated diabetic cats (93 +/- 9 nm) compared to the untreated diabetic cats (114 +/- 15 nm). In addition, quantitation of endothelial cells, pericytes, and contacts between endothelial cells and pericytes in electron micrographs revealed that they were not reduced in number in untreated diabetic cats compared to normal or sulindac-treated diabetic animals.

Topics: Animals; Basement Membrane; Capillaries; Cats; Cell Count; Diabetic Retinopathy; Disease Models, Animal; Endothelium, Vascular; Image Processing, Computer-Assisted; Pancreatectomy; Reproducibility of Results; Retina; Retinal Vessels; Sulindac

Sorbitol, resulting from glucose metabolism through aldose reductase, may play a role in diabetic complications such as cataracts, neuropathy, and vasculopathy. Sulindac (Clinoril) and sorbinil, two inhibitors of aldose reductase, decreased sorbitol formation in cataract or nerve tissue incubated in high glucose TC-199 media. Sulindac, a widely used anti-rheumatic drug, may have clinical applications in preventing diabetic complications.

Topics: Aldehyde Reductase; Animals; Diabetic Neuropathies; Diabetic Retinopathy; Imidazoles; Imidazolidines; Indenes; Lens, Crystalline; Rabbits; Rats; Sciatic Nerve; Sorbitol; Sugar Alcohol Dehydrogenases; Sulindac