Oxidative stress in ARPE-19 cultures: Do melanosomes confer cytoprotection?

Zaręba, Mariusz; Raciti, Michael W.; Henry, Michele M.; Sarna, Tadeusz; Burke, Janice M.

doi:10.1016/j.freeradbiomed.2005.08.015

Cited by 60 publications

(65 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, recent studies have focused on strategies that protect RPEs from oxidative stress for the treatment of AMD. Exposure to H 2 O 2 is often used as a classic model to convey the oxidative stress susceptibility and antioxidant activity of RPEs (30,31). The present study determined the protective effects of allicin on RPEs exposed to H 2 O 2 .…”

Section: Discussionmentioning

confidence: 90%

Allicin attenuates H2O2-induced cytotoxicity in retinal pigmented epithelial cells by regulating the levels of reactive oxygen species

Zhang

Wei

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract.Retinal pigmented epithelial cell (RPE) oxidative stress is known to have a vital role in the etiology of age-related macular degeneration (AMD). The present study aimed to investigate whether allicin, a natural product with antioxidant activity, was able to protect RPEs (ARPE-19) from hydrogen peroxide (H 2 O 2 )-induced damage, and to determine the underlying mechanisms. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to determine cellular viability, and reactive oxygen species (ROS) were detected using a ROS Assay kit. The results demonstrated that allicin was able to protect ARPE-19 cells from H 2 O 2 -induced damage in a dose-dependent manner. In addition, allicin attenuated oxidative stress by reducing the levels of intracellular ROS and malondialdehyde (MDA), and enhancing the glutathione/glutathione disulfide (GSSG) ratio. With regards to the underlying mechanism, allicin was able to markedly modulate the expression levels of ROS-associated enzymes, including superoxide dismutase, NADPH oxidase 4 and NAD(P)H dehydrogenase quinone 1, and elevate the activity of nuclear factor erythroid 2-related factor 2 in the H 2 O 2 -stimulated ARPE-19 cells. These results suggested that allicin may exert protective effects against H 2 O 2 -induced cytotoxicity in RPEs via ROS regulation.

show abstract

Section: Discussionmentioning

confidence: 90%

Allicin attenuates H2O2-induced cytotoxicity in retinal pigmented epithelial cells by regulating the levels of reactive oxygen species

Zhang

Wei

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…Juxtaposed between the photoreceptors apically and the choroiocapillaris basally, this epithelium is continuously bombarded by high levels of oxidants [43,44]. Among its numerous function, it constitutes the blood retinal barrier, facilitates selective transport between the choroidal vasculature and the outer retina, phagocytoses and degrades shed photoreceptor outer segments, regenerates photopigments, secretes neurotrophic, adhesion, and vascular regulatory factors, and contributes to the functional integrity of Bruch's membrane and the choriocapillaris.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

Burke

et al. 2010

j ocul biol dis inform

Self Cite

View full text Add to dashboard Cite

Impairment of mitochondria function and cellular antioxidant systems are linked to aging and neurodegenerative diseases. In the eye, the retinal pigment epithelium (RPE) is exposed to a highly oxidative environment that contributes to age-related visual dysfunction. Here, we examined changes in mitochondrial function in human RPE cells and sensitivity to oxidative stress with increased chronological age. Primary RPE cells from young (9-20)-, mid-age (48-60)-, and >60 (62-76)-year-old donors were grown to confluency and examined by electron microscopy and flow cytometry using several mitochondrial functional assessment tools. Susceptibility of RPE cells to H 2 O 2 toxicity was determined by lactate dehydrogenase and cytochrome c release, as well as propidium iodide staining. Reactive oxygen species, cytoplasmic Ca 2+ [Ca 2+ ] c , and mitochondrial Ca 2+ [Ca 2+ ] m levels were measured using 2′,7′-dichlorodihydrofluorescein diacetate, fluo-3/AM, and Rhod-2/AM, respectively, adenosine triphosphate (ATP) levels were measured by a luciferin/luciferase-based assay and mitochondrial membrane potential (ΔΨm) estimated using 5,5′,6,6′-tetrachloro 1,1′3,3′-tetraethylbenzimid azolocarbocyanine iodide. Expression of mitochondrial and antioxidant genes was determined by real-time polymerase chain reaction. RPE cells show greater sensitivity to oxidative stress, reduction in expression of mitochondrial heat shock protein 70, uncoupling protein 2, and superoxide dismutase 3, and greater expression of superoxide dismutase 2 levels with increased chronological age. Changes in mitochondrial number, size, shape, matrix density, cristae architecture, and membrane integrity were more prominent in samples obtained from >60 years old compared to midage and younger donors. These mitochondria abnormalities correlated with lower ATP levels, reduced ΔΨm, decreased [Ca 2+ ] c , and increased sequestration of [Ca 2+ ] m in cells with advanced aging. Our study provides evidence for mitochondrial decay, bioenergetic deficiency, weakened antioxidant defenses, and increased sensitivity of RPE cells to oxidative stress with advanced aging. Our findings suggest that with increased severity of mitochondrial decay and oxidative stress, RPE function may be altered in some individuals in a way that makes the retina more susceptible to age-related injury.

show abstract

“…Melanin primarily acts as an absorbent of incoming photons that have passed the photoreceptor layer, thereby preventing intraocular light scattering that otherwise may reduce visual acuity. In addition, it has also been shown to possess anti-oxidant properties by scavenging free radicals and, possibly, also due to chelation of transition metals such as iron and copper [137,138].…”

Section: Free Radical Scavengersmentioning

confidence: 99%

Oxidative stress-related damage of retinal pigment epithelial cells : possible protective properties of autophagocytosed iron-binding proteins

Karlsson¹

2015

View full text Add to dashboard Cite

Oxidative stress in ARPE-19 cultures: Do melanosomes confer cytoprotection?

Cited by 60 publications

References 56 publications

Allicin attenuates H2O2-induced cytotoxicity in retinal pigmented epithelial cells by regulating the levels of reactive oxygen species

Allicin attenuates H2O2-induced cytotoxicity in retinal pigmented epithelial cells by regulating the levels of reactive oxygen species

Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

Oxidative stress-related damage of retinal pigment epithelial cells : possible protective properties of autophagocytosed iron-binding proteins

Contact Info

Product

Resources

About