RPE barrier breakdown in diabetic retinopathy: seeing is believing

Xu, Huizhuo; Song, Zhiming; Fu, Su; Zhu, Meili; Le, Yun-Zheng

doi:10.1007/s12177-011-9068-4

Cited by 82 publications

(65 citation statements)

References 79 publications

(115 reference statements)

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“…81 Diabetes has been found to affect many of these functions, but the contribution of the RPE to the pathogenesis of DR remained largely unknown. Nevertheless, several abnormalities induced in RPE in diabetes (excessive production of vascular endothelial growth factor, subnormal production of pigment epithelium-derived factor, 82 and increased permeability across the RPE, 83,84 potentially allowing excessive water influx into the retina 83 ) have a clear relationship with the retinopathy.…”

Section: Rpe Datamentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

171

147

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Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe changes involving metabolic abnormalities secondary to hyperglycemia, oxidative stress, and activation of transcription factors, together with neuroglial alterations in the diabetic retina. Changes in biochemical pathways and how they promote pathophysiologic developments involving proinflammatory cytokines, chemokines, and adhesion molecules are discussed. Inflammation-mediated leukostasis, retinal ischemia, and neovascularization and their contribution to pathological and clinical stages leading to vision loss in diabetic retinopathy (DR) are highlighted. In addition, potential treatment strategies involving fibrates, connexins, neuroprotectants, photobiomodulation, and anti-inflammatory agents against the development and progression of DR lesions are reviewed. The importance of appropriate animal models for testing novel strategies against DR lesions is discussed; in particular, a novel nonhuman primate model of DR and the suitability of rodent models are weighed. The purpose of this review is to highlight our current understanding of the pathogenesis of DR and to summarize recent advances using novel approaches or targets to investigate and inhibit the retinopathy. (Am J Pathol 2017, 187: 9e19; http://dx

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Section: Rpe Datamentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

171

147

View full text Add to dashboard Cite

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“…RPE cells are one of the main constituents of the blood-retinal barrier (BRB) and alterations in this structure play a central role in the development of retinal diseases, including DR [26,27]. D407 RPE cells are a spontaneously transformed cell line that was previously obtained by others from a primary culture of human RPE cells [28].…”

Section: Our Data Demonstrate That Retinas From the Ins2mentioning

confidence: 99%

Oxidative stress modulates the expression of VEGF isoforms in the diabetic retina

Simão¹,

Bitoque²,

Silva³

2016

New Front Ophthalmol

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Change in levels of vascular endothelial growth factors (VEGF) isoforms is a feature of diabetic retinopathy. To better characterize the expression of VEGFa and VEGF 165 b isoforms in the diabetic retina and to explore how oxidative stress influences the balance between these molecules, we have used the Ins2 Akita mouse model of diabetes. Retinal tissue collected from wild-type and Ins2Akita mice, together with D407 retinal pigment epithelial (RPE) cells were used as experimental models. The retina of the Ins2Akita diabetic mice was shown to have decreased levels of the anti-angiogenic VEGF 165 b protein and a high production of reactive oxygen species (ROS). High glucose deregulated the expression of VEGF proteins as well as the production of ROS in RPE cells. Physiological levels of H 2 O 2 were found to preserve the equilibrium between VEGF isoforms in RPE cells while pathological levels down-regulated the VEGF 165 b. Besides hyperglycemia, oxidative stress also contributes to disrupt the equilibrium between pro-and anti-angiogenic factors in the retina, a profile frequently found in retinal pathologies.Abbreviations: AMD -age-related macular degeneration; BRB -blood-retinal barrier; DR -diabetic retinopathy; PEDF -pigment epithelium-derived; factor RPE -retinal pigment epithelial; ROSreactive oxygen species; VEGF -vascular endothelial growth factor

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“…Nearly all types of retinal cells are at risk. Notable among these cells are retinal pigment epithelium (RPE), which performs a number of vital functions to maintain the overall health of the retina, such as transport of nutrients and removal of waste products from photoreceptor cells, retinoid transport and regeneration, and immune/inflammation [9,10]. RPE is located between the photoreceptors and the choriocapillaries, which constitutes the outer blood-retina barrier.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Autophagy by High Glucose in Human Retinal Pigment Epithelium

Yao

Tao

et al. 2014

Cell Physiol Biochem

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Background: Autophagy is a self-degradative process that is important for balancing sources of energy at critical times in development and in response to nutrient stress. Retinal pigment epithelium (RPE) works as the outer blood retina barrier and is vulnerable to energy stress-induced injury. However, the effect of high glucose treatment on autophagy is still unclear in RPE. Methods: Transmission electron microscopy was used to detect the generation of autophagosome. Small interfering RNA (siRNA) and MTT was used to determine the effect of autophagy on cell viability. Western blots and immunohistochemistry were used to detect the expression pattern of autophagic markers, including LC3 and p62. Results: High glucose treatment results in a significant increase in the generation of autophagosome and altered expression of LC3 and p62. High glucose-induced autophagy is independent of mTOR signaling, but is mainly regulated via ROS-mediated ER stress signaling. Conclusion: In the scenario of high glucose-induced oxidative stress, autophagy may be required for the removal of damaged proteins, and provide a default mechanism to prevent high glucose-induced injury in RPE. © 2014 S. Karger AG, Basel

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RPE barrier breakdown in diabetic retinopathy: seeing is believing

Cited by 82 publications

References 79 publications

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Oxidative stress modulates the expression of VEGF isoforms in the diabetic retina

Regulation of Autophagy by High Glucose in Human Retinal Pigment Epithelium

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