Pigment Epithelium-derived Factor Protects Retinal Pigment Epithelial Cells Against Cytotoxicity “In Vitro”

Nadal-Nicolás, Francisco M.; Becerra, S. Patricia

doi:10.1007/978-3-319-75402-4_56

Cited by 17 publications

(9 citation statements)

References 31 publications

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“…The pathological mechanism underlying AMD has not yet been completely elucidated, and the condition remains untreatable at present. Sodium iodate (NaIO 3 ), an oxidative toxic agent, causes selective RPE cell damage and can reportedly serve as a reproducible in vitro and in vivo model of AMD [ 15 , 16 , 17 , 18 ]. NaIO 3 at a concentration of ≥10 mM activates caspase 3/7/8-dependent apoptosis and caspase-independent cell necroptosis, leading to the apoptosis of RPE cells [ 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway

Chang

Lee

Hsu

et al. 2021

IJMS

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Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.

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Section: Introductionmentioning

confidence: 99%

Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway

Chang

Lee

Hsu

et al. 2021

IJMS

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“…RPE derived growth factors include pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF)[ 17 ], basic fibroblast growth factor (FGF-2), epidermal growth factor (EGF), and nerve growth factor (NGF)[ 8 , 12 , 18 ]. Both FGF-2 and EGF have been shown to generate retinal neurons from human retinal precursor cells[ 19 ].…”

Section: Discussionmentioning

confidence: 99%

ARPE-19 conditioned medium promotes neural differentiation of adipose-derived mesenchymal stem cells

Mannino¹,

Cristaldi²,

Giurdanella³

et al. 2021

WJSC

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BACKGROUND Adipose-derived stem cells (ASCs) have been increasingly explored for cell-based medicine because of their numerous advantages in terms of easy availability, high proliferation rate, multipotent differentiation ability and low immunogenicity. In this respect, they have been widely investigated in the last two decades to develop therapeutic strategies for a variety of human pathologies including eye disease. In ocular diseases involving the retina, various cell types may be affected, such as Müller cells, astrocytes, photoreceptors and retinal pigment epithelium (RPE), which plays a fundamental role in the homeostasis of retinal tissue, by secreting a variety of growth factors that support retinal cells. AIM To test ASC neural differentiation using conditioned medium (CM) from an RPE cell line (ARPE-19). METHODS ASCs were isolated from adipose tissue, harvested from the subcutaneous region of healthy donors undergoing liposuction procedures. Four ASC culture conditions were investigated: ASCs cultured in basal Dulbecco's Modified Eagle Medium (DMEM); ASCs cultured in serum-free DMEM; ASCs cultured in serum-free DMEM/F12; and ASCs cultured in a CM from ARPE-19, a spontaneously arising cell line with a normal karyotype derived from a human RPE. Cell proliferation rate and viability were assessed by crystal violet and MTT assays at 1, 4 and 8 d of culture. At the same time points, ASC neural differentiation was evaluated by immunocytochemistry and western blot analysis for typical neuronal and glial markers: Nestin, neuronal specific enolase (NSE), protein gene product (PGP) 9.5, and glial fibrillary acidic protein (GFAP). RESULTS Depending on the culture medium, ASC proliferation rate and viability showed some significant differences. Overall, less dense populations were observed in serum-free cultures, except for ASCs cultured in ARPE-19 serum-free CM. Moreover, a different cell morphology was seen in these cultures after 8 d of treatment, with more elongated cells, often showing cytoplasmic ramifications. Immunofluorescence results and western blot analysis were indicative of ASC neural differentiation. In fact, basal levels of neural markers detected under control conditions significantly increased when cells were cultured in ARPE-19 CM. Specifically, neural marker overexpression was more marked at 8 d. The most evident increase was observed for NSE and GFAP, a modest increase was observed for nestin, and less relevant changes were observed for PGP9.5. CONCLUSION The presence of growth factors produced by ARPE-19 cells in tissue culture induces ASCs to express neural differentiation markers typical of the neuronal and glial cells of the retina.

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“…Pretreatment with PEDF protects retinal neurons from H 2 O 2 -induced apoptosis in a dose-response relationship with a half effective dose of 50 ng/ml [22]. In an oxidative damage model of RPE cells (ARPE-19 cell line) cultured in vitro, adding 5nM and 10nM PEDF could reduce about 50% cytotoxicity induced by NaIO 3 [24]. In addition, the protective effect of PEDF on photo retina is related to the calcium-mediated PKC pathway [11].…”

Section: Discussionmentioning

confidence: 99%

TRPM7 ameliorates the blue light-induced apoptosis of RPE cells involving PKC/ERK

2020

Preprint

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Background Blue light triggers apoptosis of retinal pigment epithelium (RPE) cells and causes retinal damage. The aim of this study was to elucidate the protective role of TRPM7 in photo-damaged RPE cells. Methods RPE cells isolated from Sprague-Dawley (SD) rats were cultured in vitro , and exposed to varying intensities of blue light (500-5000 Lux). Cell proliferation and viability were respectively assessed by BrdU incorporation and MTT assays. Real-time PCR and Western blotting were used to analyze the mRNA and protein expression levels of TRPM7, PKC, ERK and Bax/Bcl-2. The cells were transfected with TRPM7 siRNA to knockdown its mRNA levels, or transduced with TRPM7–overexpressing lentiviruses. Pigment epithelium-derived factor (PEDF) was used in combination to detect the anti apoptosis effect. Results Blue light inhibited the proliferation and viability of RPE cells in an intensity-de pendent manner when compared to non-irradiated controls ( P <0.05). Compared to the control, photo-damaged RPE cells showed decreased levels of TRPM7, PKC, ERK and Bax, increased in Bcl-2 ( P <0.01) . Forced expression of TRPM7 partially ameliorated the reduction of proliferation and viability of RPE cells( P <0.01), alleviated the downregulation of TRPM7, PKC, ERK and Bax expression levels( P <0.01), induced by blue light irradiation, while TRPM7 knockdown had opposite effects( P <0.01). TRPM7 and PEDF synergistically alleviated the damaging effects of blue light. Conclusions The apoptosis of RPE cells induced by blue light was positively correlated with the expression of TRPM7. Forced expression of TRPM7 partially attenuated the deleterious effects of blue-light-demaged RPE cells and showed a synergistic protective effect with PEDF, involving PKC/ERK signaling pathway.

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Pigment Epithelium-derived Factor Protects Retinal Pigment Epithelial Cells Against Cytotoxicity “In Vitro”

Cited by 17 publications

References 31 publications

Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway

Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway

ARPE-19 conditioned medium promotes neural differentiation of adipose-derived mesenchymal stem cells

TRPM7 ameliorates the blue light-induced apoptosis of RPE cells involving PKC/ERK

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