Significance of Outer Blood–Retina Barrier Breakdown in Diabetes and Ischemia

Xu, Huizhuo; Le, Yun-Zheng

doi:10.1167/iovs.10-6518

Cited by 162 publications

(132 citation statements)

References 28 publications

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“…Therefore, we verified the tight junction integrity in ischemic and diabetic mice, which was shown to have a significant upregulation of their retinal VEGF [31,41]. The loss of tight junction integrity in the RPE, as judged by immunohistochemical staining of occludin, was apparent in ischemic and diabetic mice [32]. Early studies showed that serum inhibited the formation of tight junctions and reduced the expression of ZO-1 in RPE cultures derived from the Royal College of Surgeons' rats [61,62].…”

Section: Regulations Of Rpe Barrier Functionsmentioning

confidence: 85%

“…The tight junctions in both the endothelial and RPE barriers are compromised in DR [30][31][32]. Diabetes and hypoxia (occurred in late stage of DR) induce the breakdown of the RPE barrier [24,32].…”

Section: Alterations Of the Rpe In Diabetesmentioning

confidence: 99%

“…Diabetes and hypoxia (occurred in late stage of DR) induce the breakdown of the RPE barrier [24,32]. The ultrastructural changes in the RPE in early stage of diabetes can be readily detected in experimental animals by electron microscopy [33][34][35].…”

Section: Alterations Of the Rpe In Diabetesmentioning

confidence: 99%

“…To evaluate the significance of the diabetes-induced RPE barrier breakdown and to establish a quantitative assay for the RPE barrier-specific leakage, we recently developed a method to identify macromolecules leaked through the RPE barrier de novo in diabetic and ischemic rodents [32]. Immediately after injecting 40 kDa FITC-dextran intravenously to mice 12 months after the onset of diabetes, we detected strong fluorescent signals next to the RPE (Fig.…”

Section: Fluorescent Microscopic Imaging Of Rpe Barrier Breakdown Inmentioning

confidence: 99%

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RPE barrier breakdown in diabetic retinopathy: seeing is believing

Song

et al. 2011

j ocul biol dis inform

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Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness in working-age Americans. DR is traditionally regarded as a disorder of blood-retina barriers, and the leakage of blood content is a major pathological characteristic of the disease. While the breakdown of the endothelial barrier in DR has been investigated extensively, the vascular leakage through the retinal pigment epithelium (RPE) barrier in the disease has not been widely acknowledged. As the blood content leaked through the RPE barrier causes excessive water influx to the retina, the breakdown of the RPE barrier is likely to play a causative role in the development of some forms of diabetic macular edema, a major cause of vision loss in DR. In this article, we will discuss the clinical evidences of the diabetes-induced RPE barrier breakdown, the alteration of the RPE in diabetes, the molecular and cellular mechanism of RPE barrier breakdown, and the research tools for the analysis of RPE barrier leakage. Finally, we will discuss the methodology and potential applications of our recently developed fluorescent microscopic imaging for the diabetes-or ischemia-induced RPE barrier breakdown in rodents.

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Section: Regulations Of Rpe Barrier Functionsmentioning

confidence: 85%

Section: Alterations Of the Rpe In Diabetesmentioning

confidence: 99%

Section: Alterations Of the Rpe In Diabetesmentioning

confidence: 99%

Section: Fluorescent Microscopic Imaging Of Rpe Barrier Breakdown Inmentioning

confidence: 99%

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RPE barrier breakdown in diabetic retinopathy: seeing is believing

Song

et al. 2011

j ocul biol dis inform

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“…The outer BRB is responsible for approximately 80% of the oxygen supply in the eye. 47 A number of independent studies have demonstrated outer BRB breakdown in diabetes and ischemia. 48,49 Overexpression of VEGF has been shown to play a key pathogenic role in breakdown of the barrier and contributes to impaired tight-junction integrity in the outer BRB.…”

Section: Discussionmentioning

confidence: 99%

Impacts of Hypoxia-Inducible Factor-1 Knockout in the Retinal Pigment Epithelium on Choroidal Neovascularization

Lin¹,

Hu²,

Chen³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Hypoxia-inducible factor (HIF)-1 is a key oxygen sensor and is believed to play an important role in neovascularization (NV). The purpose of this study is to determine the role of retinal pigment epithelium (RPE)-derived HIF-1a on ocular NV. METHODS.Conditional HIF-1a knockout (KO) mice were generated by crossing transgenic mice expressing Cre in the RPE with HIF-1a floxed mice, confirmed by immunohistochemistry, Western blot analysis, and fundus fluorescein angiography. The mice were used for the oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models.RESULTS. HIF-1a levels were significantly decreased in the RPE layer of ocular sections and in primary RPE cells from the HIF1a KO mice. Under normal conditions, the HIF-1a KO mice exhibited no apparent abnormalities in retinal histology or visual function as shown by light microscopy and electroretinogram recording, respectively. The HIF-1a KO mice with OIR showed no significant difference from the wild-type (WT) mice in retinal levels of HIF-1a and VEGF as well as in the number of preretinal neovascular cells. In the laser-induced CNV model, however, the disruption of HIF-1a in the RPE attenuated the over expression of VEGF and the intercellular adhesion molecule 1 (ICAM-1), and reduced vascular leakage and CNV area.CONCLUSIONS. RPE-derived HIF-1a plays a key role in CNV, but not in ischemia-induced retinal NV. (Invest Ophthalmol Vis Sci.

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The Relationship of Central Foveal Thickness to Urinary Iodine Concentration in Retinitis Pigmentosa With or Without Cystoid Macular Edema

et al. 2014

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IMPORTANCE Current treatments for cystoid macular edema (CME) in retinitis pigmentosa (RP) are not always effective, may lead to adverse effects, and may not restore visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce CME in RP.OBJECTIVE To determine whether central foveal thickness (CFT) in the presence of CME is related to dietary iodine intake inferred from urinary iodine concentration (UIC) in nonsmoking adults with RP. DESIGN, SETTING, AND PARTICIPANTSWe performed a cross-sectional observational study of 212 nonsmoking patients aged 18 to 69 years referred to our institution for RP with visual acuity of no worse than 20/200 in at least 1 eye. EXPOSURE Retinitis pigmentosa with or without CME. MAIN OUTCOMES AND MEASURESWith the eye as the unit of analysis, the relationship of log CFT measured by optical coherence tomography to UIC measured from multiple spot samples and represented as a 3-level classification variable (<100, 100-199, and Ն200 μg/L), assigning greater weight to patients with more reliable UIC estimates. RESULTSAnalyses were limited to 199 patients after excluding 11 who failed to return urine samples for measuring UIC and 2 outliers for UIC. Of the 199 patients, 36.2% had CME in 1 or both eyes. Although log CFT was inversely related to UIC based on findings from all eyes (P = .02), regression of log CFT on UIC separately for eyes with and without CME showed a strong inverse significant relationship for the former group (P < .001) and no significant relationship for the latter group (P = .66) as tested. For the eyes with CME, CFT ranged from a geometric mean of 267 μm for a median UIC of less than 100 μg/L to a geometric mean of 172 μm for a median UIC of 200 μg/L or greater. In contrast, we found no significant association between CME prevalence and UIC based on the entire sample as tested (odds ratio, 1.01 [95% CI, 0.38-2.67]; P = .99).CONCLUSIONS AND RELEVANCE A higher UIC in nonsmoking adults with RP was significantly associated with less central foveal swelling in eyes with CME. Additional study is required to determine whether an iodine supplement can limit or reduce the extent of CME in patients with RP.

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Significance of Outer Blood–Retina Barrier Breakdown in Diabetes and Ischemia

Cited by 162 publications

References 28 publications

RPE barrier breakdown in diabetic retinopathy: seeing is believing

RPE barrier breakdown in diabetic retinopathy: seeing is believing

Impacts of Hypoxia-Inducible Factor-1 Knockout in the Retinal Pigment Epithelium on Choroidal Neovascularization

The Relationship of Central Foveal Thickness to Urinary Iodine Concentration in Retinitis Pigmentosa With or Without Cystoid Macular Edema

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