Regulation of Autophagy by High Glucose in Human Retinal Pigment Epithelium

Yao, Jin; Tao, Zhi‐Fu; Li, Chaopeng; Li, Xiu‐Miao; Cao, Guiying; Jiang, Qin; Yan, Biao

doi:10.1159/000356654

Cited by 53 publications

(37 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Suppression on the flux of autophagosome formation can thus protect the retinal cells from hypoxic damage. In fact, modulation of autophagy become a therapeutics target for treatment of ocular diseases such as glaucoma, diabetic retinopathy and age-related macular degeneration (AMD) [4,53,54] however, the safety and side effects of the anti-autophagic drug has been concerned [55]. Developments of novel anti-autophagic drugs that are more specific to autophagic pathway and clinically safer are emerged.…”

Section: Discussionmentioning

confidence: 99%

Lutein Attenuates Both Apoptosis and Autophagy upon Cobalt (II) Chloride-Induced Hypoxia in Rat Műller Cells

Fung

Law

2016

PLoS ONE

View full text Add to dashboard Cite

Retinal ischemia/reperfusion injury is a common feature of various retinal diseases such as glaucoma and diabetic retinopathy. Lutein, a potent anti-oxidant, is used to improve visual function in patients with age-related macular degeneration (AMD). Lutein attenuates apoptosis, oxidative stress and inflammation in animal models of acute retinal ischemia/hypoxia. Here, we further show that lutein improved Műller cell viability and enhanced cell survival upon hypoxia-induced cell death through regulation of intrinsic apoptotic pathway. Moreover, autophagy was activated upon treatment of cobalt (II) chloride, indicating that hypoxic injury not only triggered apoptosis but also autophagy in our in vitro model. Most importantly, we report for the first time that lutein treatment suppressed autophagosome formation after hypoxic insult and lutein administration could inhibit autophagic event after activation of autophagy by a pharmacological approach (rapamycin). Taken together, lutein may have a beneficial role in enhancing glial cell survival after hypoxic injury through regulating both apoptosis and autophagy.

show abstract

Section: Discussionmentioning

confidence: 99%

Lutein Attenuates Both Apoptosis and Autophagy upon Cobalt (II) Chloride-Induced Hypoxia in Rat Műller Cells

Fung

Law

2016

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…HG induces ROS production as well as p38 and extracellular signal-regulated kinase (ERK) activation in RPE cells which cause apoptosis [12, 16]. In hyperglycemic conditions, mitochondrial damage and ER stress are major factors that trigger apoptosis leading to death of a several different cell types in the retina including pericytes, vascular endothelial cells, and cells of the pigmented epithelium [10, 11, 14, 15]. ROS is thought to be involved in mitochondrial damage and ER stress [15, 38, 46].…”

Section: Discussionmentioning

confidence: 99%

Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells

Chang

Snow

LaBarbera

et al. 2015

Chemico-Biological Interactions

View full text Add to dashboard Cite

Chronic hyperglycemia is an important risk factor involved in the onset and progression of diabetic retinopathy (DR). Among other effectors, aldose reductase (AR) has been linked to the pathogenesis of this degenerative disease. The purpose of this study was to investigate whether the novel AR inhibitor, beta-glucogallin (BGG), can offer protection against various hyperglycemia-induced abnormalities in human adult retinal pigment epithelia (ARPE-19) cells. AR is an enzyme that contributes to cellular stress by production of reactive oxygen species (ROS) under high glucose conditions. A marked decrease in cell viability (from 100% to 78%) following long-term exposure (4 days) of RPE cells to high glucose (HG) was largely prevented by siRNA-mediated knockdown of AR gene expression (from 79% to 97%) or inhibition using sorbinil (from 66% to 86%). In HG, BGG decreased sorbitol accumulation (44%), ROS production (27%) as well as ER stress (22%). Additionally, we demonstrated that BGG prevented loss of mitochondrial membrane potential (MMP) under HG exposure. We also showed that AR inhibitor pretreatment reduced retinal microglia-induced apoptosis in APRE-19 cells. These results suggest that BGG may be useful as a therapeutic agent against retinal degeneration in the diabetic eye by preventing RPE cell death.

show abstract

“…High blood glucose levels also trigger autophagy to prevent glucose-induced damage in the RPE. In this scenario, autophagy is mainly regulated through ROS-mediated ER stress instead of through the mTOR signalling pathway 36. Moreover, a damaged blood-retina barrier releases cytoplasmic lipoproteins, and extra-vascular modified LDL promotes RPE damage through ER stress, oxidative stress, apoptosis and autophagy.…”

Section: Introduction To Autophagymentioning

confidence: 99%

The Evolving Functions of Autophagy in Ocular Health: A Double-edged Sword

Chai

Zhang

et al. 2016

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Autophagy plays an adaptive role in cell survival, development, differentiation and intracellular homeostasis. Autophagy is recognized as a 'self-cannibalizing' process that is active during stresses such as starvation, chemotherapy, infection, ageing, and oxygen shortage to protect organisms from various irritants and to regenerate materials and energy. However, autophagy can also lead to a form of programmed cell death distinct from apoptosis.Components of the autophagic pathway are constitutively expressed at a high level in the eye, including in the cornea, lens, retina, and orbit. In addition, the activation of autophagy is directly linked to the development of eye diseases such as age-related macular degeneration (ARMD), cataracts, diabetic retinopathy (DR), glaucoma, photoreceptor degeneration, ocular tumours, ocular infections and thyroid-associated ophthalmopathy (TAO). A high level of autophagy defends against external stress; however, excessive autophagy can result in deterioration, as observed in ocular diseases such as ARMD and DR.This review summarizes recent developments elucidating the relationship between autophagy and ocular diseases and the potential roles of autophagy in the pathogenesis and treatment of these diseases.

show abstract

Regulation of Autophagy by High Glucose in Human Retinal Pigment Epithelium

Cited by 53 publications

References 28 publications

Lutein Attenuates Both Apoptosis and Autophagy upon Cobalt (II) Chloride-Induced Hypoxia in Rat Műller Cells

Lutein Attenuates Both Apoptosis and Autophagy upon Cobalt (II) Chloride-Induced Hypoxia in Rat Műller Cells

Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells

The Evolving Functions of Autophagy in Ocular Health: A Double-edged Sword

Contact Info

Product

Resources

About