Breakdown of the Inner and Outer Blood Retinal Barrier in Streptozotocin-Induced Diabetes

Abstract

Using vitreous fluorophotometry and quantitative fluorescence microscopy the authors studied the permeability of the blood-retinal barrier (BRB) to fluorescein in control and in 8 days streptozotocin-induced diabetic rats. Vitreous fluorophotometry showed that fluorescein permeates BRB in control and in diabetic rats. However, in diabetic rats the permeability to fluorescein was significantly increased as compared to control rats. The vitreous penetration ratio (VPR) values for total and free fluorescein at 60 min, were higher for diabetic rats (231.2+/-12.9 min-1 for total fluorescein and 1299.24+/-58.0 min-1 for free fluorescein) than for control rats (95.5+/-3.5 min-1 for total fluorescein and 646.6+/-55. 0 min-1 for free fluorescein) (P<0.05). Quantitative confocal fluorescence microscopy confirmed these findings and identified the site of leakage across the BRB by comparing the relative importance of the fluorescein leakage across the outer and inner BRB. In control rats the fluorescence levels remained relatively low in the photoreceptor layer, next to the outer BRB but in the inner nuclear layer, next to the inner BRB reached values that were almost ten times higher. These results suggest that in retinas of control rats fluorescein penetrates predominantly through the inner BRB. In diabetic rats the fluorescence levels in the photoreceptor and in the inner nuclear layer were significantly increased as compared to the fluorescence levels in controls rats. Nevertheless, in the inner nuclear layer the fluorescence levels were also generally higher than the fluorescence levels at the photoreceptor layer. The rates of fluorescence levels between the inner nuclear layer and the photoreceptor layer were apparently 3:1, 60 min after the single intravenous injection of fluorescein. Also, the fluorescein penetration in the inner nuclear layer of the diabetic rats is higher than that observed in the inner nuclear layer of the control rats (P<0.001). These findings suggest that the permeability to fluorescein of both components of the BRB is increased 8 days after the induction of diabetes by streptozotocin and that the permeability of the retinal vasculature is preferentially affected.

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

“…The main cause for this increase could be the breakdown of the blood-retinal barrier, especially the inner one, and the subsequent edematous swelling, in agreement with other studies [15,16,17]. Therefore, a gradual decrease in the thickness of the inner retina, to well below that observed in the normal state, seems likely to arise from the decay of the neural components affected by the altered biochemical environment, including the glucose transport system [18,19].…”

Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein

“…activator protein-1 have been shown to be partially responsible for MCP-1 regulation . Previous studies have demonstrated that oxidized LDL and glycoxidized LDL are potent inducers of NF-kB activation in vascular cells and monocyte/macrophages (Do carmo et al 1998, Sonoki et al 2002. Moreover, the results from electrophoretic mobility shift assay and chromatin immunoprecipitation assays showed that oxidized glycated LDL and oxidized LDL induced MCP-1 expression via NF-kB activation.…”

Effect of a single intravitreal bevacizumab injection on different optical coherence tomographic patterns of diabetic macular oedema

“…What is apparent is that the multifactorial disruption of inner and outer blood-retinal barriers leads to abnormal inflow of fluid into the neurosensory retina exceeding the outflow, ending up with intraretinal and subretinal fluid accumulation. [1][2][3][4] Besides making the objective diagnosis and quantitative evaluation of macular oedema possible, optical coherence tomography (OCT) offers the opportunity to assess in vivo histologic cross-sections of the healthy and diseased retina, leading to a better understanding of pathologic processes. 5,6 Three different morphologic subtypes of macular oedema were defined according to OCT: 7,8 Sponge-like diffuse retinal thickening (DRT), cystoid macular oedema (CMO) and serous retinal detachment (SRD).…”