Effect of Sulindac on the Permeability of the Blood-Retinal Barrier in Early Diabetic Retinopathy

Cunha-Vaz, Josè; Mota, Carolina C.; Leite, E.; Abreu, J R de; Ruas, Manuel A.

doi:10.1001/archopht.1985.01050090059032

Cited by 37 publications

(9 citation statements)

References 18 publications

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“…AR inhibitors can largely prevent diabetes-or galactosaemia-associated structural changes in the retinal vasculature and the RPE (Frank et al, 1983;Robison et al, 1983Robison et al, , 1989) and breakdown of the BRB in diabetic and galactosaemic rats (Cunha-Vaz et al, 1985;Lightman et al, 1987;Williamson et al, 1987;Vinores et al, 1990b, c). AR has been demonstrated by light microscopy in diabetic human retina and RPE, and its expression correlates with the severity and duration of the disease (Vinores et al, 1988), but AR has not previously been demonstrated in RVE cells, which are the primary cells to lose their barrier function in diabetic retinopathy.…”

mentioning

confidence: 45%

Electron microscopic immunocytochemical demonstration of blood-retinal barrier breakdown in human diabetics and its association with aldose reductase in retinal vascular endothelium and retinal pigment epithelium

et al. 1993

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Light-microscopic immunohistochemical staining for albumin has been used to localize sites of blood-retinal barrier (BRB) breakdown in ocular disorders, but the mechanism for BRB compromise cannot be resolved at this level. Using eyes up to 2 days post-mortem from normal patients or from patients with diabetic retinopathy, or other disorders known to cause BRB failure, electron-microscopic immunocytochemistry reveals focal breakdown of the inner BRB, comprised of the retinal vascular endothelium (RVE), which appears to be mediated by diffuse permeation of the RVE cells and by vesicular transport. Permeation of the retinal pigmented epithelial (RPE) cells that comprise the outer BRB also occurs, but there is no evidence of opening of tight junctions between RVE or RPE in any of the disorders evaluated. Increased aldose reductase (AR) expression in the RVE and RPE cells of diabetics as well as in the perivascular retinal astrocytes, which interact with RVE cells to establish the inner BRB, suggests that AR activity and the subsequent intracellular accumulation of sorbitol in these cell types may impair the function of the BRB in diabetes.

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confidence: 45%

Electron microscopic immunocytochemical demonstration of blood-retinal barrier breakdown in human diabetics and its association with aldose reductase in retinal vascular endothelium and retinal pigment epithelium

et al. 1993

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“…Indeed, the angiotensin-convert ing enzyme inhibitor captopril, and antihypertensive agent, improves albuminuria, even in normotensive diabetic pa tients [3] and appeared to be associated with a better prog nosis with regard to diabetic nephropathy [4], In the eyes, the permeability of the blood-retina barrier, as assessed by vitreous fluorophotometry, is used to measure vascular per meability. In the past, several small-scale intervention stud ies have been performed with vitreous fluorophotometry as the primary efficacy parameter, some with positive [5][6][7][8] but others with negative results [9,10]. However, vitreous fluorophotometry is a difficult and time-consuming meth od, necessitating specialized equipment and staff, and is therefore not suitable for large-scale application.…”

Section: Introductionsupporting

confidence: 42%

“…Table 5 summarizes these studies. Cunha-Vaz et al demonstrated an effect of long-term administration o f sulindac (a non-ste roidal anti-inflammatory drug) [5] and of sorbinil (an al dose reductase inhibitor) [6]. Parving et al [7], in an un- n.a.…”

Section: Discussionmentioning

confidence: 43%

“…In contrast, van Gerven [9] found a (sta tistically non-significant) increase in the blood-retina per meability in a group of diabetic patients treated with the al dose reductase inhibitor tolrestat. The authors discuss that their results seem to contradict those of the two studies per formed by Cunha-Vaz et al [5,6], with sulindac and sorbinil. both agents with aldose-reductase-inhibiting properties.…”

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confidence: 42%

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Reproducibility of Vitreous Fluorophotometry in Patients with Type 1 Diabetes Mellitus

Jäger¹,

Tromp

Hooymans

et al. 1997

Ophthalmologica

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We assessed the day-to-day reproducible of vitreous fluorophotometry in 7 type 1 diabetic patients and in 1 healthy control subject. The coefficient of variation for duplicate measurements was 33.7,40.3 and 23.6%, for the right eyes, the left eyes and mean values of both eyes, respectively. Assessment of reproducibility in 1 healthy subject, measured 4 times, resulted in coefficients of variation of about 60%. These values are somewhat worse than those obtained by others in healthy subjects. Since technical problems do not seem to play a significant role in this regard, our reproducibility results reflect the true biological variability of the permeability of the blood-retina barrier assessed by vitreous fluorophotometry in diabetic patients. This variability is substantial. Therefore, we conclude that this method is not precise enough to be used in intervention studies with a limited number of subjects.

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“…Administration of sulindac or sorbinil for periods of six months has been shown to stabilise the blood-retinal barrier in early diabetic retinopathy [5,6], but serious adverse reactions have been reported in association with these compounds although our clinical trials did not reveal major side effects. Freedom from side effects is especially necessary in drugs for early diabetic retinopathy, because such drugs are liable to be used for a long time, the patients are symptom-free and at last the disease is unpredictable.…”

Section: Introductionmentioning

confidence: 40%

Effect of calcium dobesilate on the blood-retinal barrier in early diabetic retinopathy

et al. 1990

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The effect of calcium dobesilate on the alteration of the blood-retinal barrier was studied in 41 adult-onset, non-insulin dependent diabetic patients with minimal or no retinopathy, randomly assigned to receive either oral calcium dobesilate (1000 mg twice daily) or a placebo for 12 months. The posterior vitreous value and the penetration ratio, determined by vitreous fluorophotometry, reflected stabilisation of blood-retinal barrier permeability in the calcium dobesilate patients and deterioration of blood retinal barrier in those given placebo. During the relatively short period of the study, one year, no significant change in microaneurysm and capillary closure gradings was observed. No side effects were associated with calcium dobesilate.

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Effect of Sulindac on the Permeability of the Blood-Retinal Barrier in Early Diabetic Retinopathy

Cited by 37 publications

References 18 publications

Electron microscopic immunocytochemical demonstration of blood-retinal barrier breakdown in human diabetics and its association with aldose reductase in retinal vascular endothelium and retinal pigment epithelium

Electron microscopic immunocytochemical demonstration of blood-retinal barrier breakdown in human diabetics and its association with aldose reductase in retinal vascular endothelium and retinal pigment epithelium

Reproducibility of Vitreous Fluorophotometry in Patients with Type 1 Diabetes Mellitus

Effect of calcium dobesilate on the blood-retinal barrier in early diabetic retinopathy

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