Fenofibric Acid Reduces Fibronectin and Collagen Type IV Overexpression in Human Retinal Pigment Epithelial Cells Grown in Conditions Mimicking the Diabetic Milieu: Functional Implications in Retinal Permeability

Trudeau, Kyle; Roy, Soma; Guo, Wen; Hernández, Cristina; Villarroel, Marta; Simó, Rafael; Roy, Sayon

doi:10.1167/iovs.11-7282

Cited by 61 publications

(58 citation statements)

References 38 publications

(46 reference statements)

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“…In ARPE-19 cells grown in high-glucose media, fenofibrate upregulated the expression of fibronectin and collagen IV, basement membrane components known to cause endothelial barrier breakdown [68]. Fenofibrate also reduced the IL-1β-induced RPE barrier permeability in ARPE-19 cultures grown in high-glucose media by suppressing adenosine monophosphate-activated protein kinase [68,69]. Interestingly, fenofibrate may have a general beneficial effect on reducing high glucose-or hypoxiainduced oxidative and ER stresses in the RPE by reducing stress-mediated signaling and by inducing autophagy and survival pathways [70].…”

Section: Regulations Of Rpe Barrier Functionsmentioning

confidence: 98%

Section: Regulations Of Rpe Barrier Functionsmentioning

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: 98%

Section: Regulations Of Rpe Barrier Functionsmentioning

confidence: 99%

RPE barrier breakdown in diabetic retinopathy: seeing is believing

Song

et al. 2011

j ocul biol dis inform

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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

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166

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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“…These mechanisms have been recently reviewed [57,60] and are summarized in Fig. (4) [61][62][63][64][65][66].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Non-Traditional Systemic Treatments for Diabetic Retinopathy: An Evidence-Based Review

Simó

Ballarini²,

Cunha‐Vaz³

et al. 2015

CMC

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Abstract:The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising. This up-to-date critical review of non-traditional systemic treatments for DR is based on the published evidence in MEDLINE spanning 1980-December 2014. It discusses a number of therapeutic options, paying particular attention to the mechanisms of action and the clinical evidence for the use of renin-angiotensin system blockade, fenofibrate and calcium dobesilate monohydrate in DR.

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Fenofibric Acid Reduces Fibronectin and Collagen Type IV Overexpression in Human Retinal Pigment Epithelial Cells Grown in Conditions Mimicking the Diabetic Milieu: Functional Implications in Retinal Permeability

Abstract: Findings from this study suggest that the downregulation of basement membrane components by FA may have a protective effect against outer blood-retinal barrier leakage associated with diabetic retinopathy.

Cited by 61 publications

References 38 publications

RPE barrier breakdown in diabetic retinopathy: seeing is believing

RPE barrier breakdown in diabetic retinopathy: seeing is believing

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Non-Traditional Systemic Treatments for Diabetic Retinopathy: An Evidence-Based Review

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