AGEs, RAGE, and Diabetic Retinopathy

Zong, Hongliang; Ward, Micheal; Stitt, Alan W.

doi:10.1007/s11892-011-0198-7

Cited by 213 publications

(162 citation statements)

References 67 publications

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“…Up-regulation of PKC results in increased vascular permeability, neovascularization, and capillary apoptosis characteristic of DR. 23 In addition, PKC increases the activity of Nox, leading to further ROS production, NF-kB activation, and inflammation, as demonstrated in animal studies. 54 However, clinical trials failed to validate that inhibition of the PKC pathway adequately inhibited the progression of DR 55 but did have effects on visual function. 56 Novel Therapeutic Approaches and Targets to Inhibit DR Recent studies examining the pathogenesis of DR are shedding light into new pharmacological approaches for inhibiting molecular alterations underlying aspects of the disease.…”

Section: Pkc Pathwaymentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

170

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: Pkc Pathwaymentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

170

147

View full text Add to dashboard Cite

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“…It has become established that chronic exposure of the retina to hyperglycemia gives rise to accumulation of advanced glycation end products ( Figure 2) that play an important role in retinopathy [29]. Advanced glycation end products (AGEs) are proteins or lipids that become nonenzymatically glycated and oxidized after exposure to aldose sugars [30].…”

Section: Accumulation Of Agesmentioning

confidence: 99%

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Safi¹,

Qvist²,

Kumar³

et al. 2013

Exp Clin Endocrinol Diabetes

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The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.

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“…It is feasible that retinal microglial activation is a normal adaptive response to retinal neurodegeneration or triggered by plasma proteins extravasating by virtue of blood-retinal barrier (BRB) breakdown. Microglial activation might be linked to hyperglycemia by the formation of advanced glycation end products (AGE) or other protein glycation products within the retina [58]. It is also possible that microglial activation is a response to systemic low-grade inflammation caused by diabetes.…”

Section: Microglial Activation In Diabetic Retinopathymentioning

confidence: 99%