scholarly journals Selective retina therapy and thermal stimulation of the retina: different regenerative properties - implications for AMD therapy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elisabeth Richert ◽  
Julia Papenkort ◽  
Claus von der Burchard ◽  
Alexa Klettner ◽  
Philipp Arnold ◽  
...  
Keyword(s):  
Cell Death ◽  
Laser Treatment ◽  
Continuous Wave ◽  
Single Cells ◽  
Thermal Stimulation ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Rpe Cells ◽  
Selective Retina Therapy ◽  
Stimulation Of

Abstract Background Selective Retina Therapy (SRT), a photodisruptive micropulsed laser modality that selectively destroys RPE cells followed by regeneration, and Thermal Stimulation of the Retina (TSR), a stimulative photothermal continuous wave laser modality that leads to an instant sublethal temperature increase in RPE cells, have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration. Methods For PCR array, 6 eyes of murine AMD models, apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively, were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation. Results TSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 h after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, 1 h after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells. Conclusions SRT induces RPE cell death, followed by regeneration within a few days. It is accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation. Both might be a therapeutic option for the treatment of AMD.

scholarly journals Selective Retina Therapy and Thermal Stimulation of the Retina: Different Regenerative Properties - Implications for AMD Therapy

2020 ◽  
Author(s):  
Elisabeth Richert ◽  
Julia Papenkort ◽  
Claus von der Burchard ◽  
Alexa Klettner ◽  
Philipp Arnold ◽  
...  
Keyword(s):  
Cell Death ◽  
Laser Treatment ◽  
Cell Damage ◽  
Single Cells ◽  
Thermal Stimulation ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Selective Retina Therapy ◽  
Age Related ◽  
Stimulation Of

Abstract BackgroundSelective Retina Therapy (SRT) and Thermal Stimulation of the Retina (TSR) have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration. MethodsFor PCR array, 6 eyes of apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation. ResultsTSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 hour after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, one hour after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells. ConclusionsSRT induces RPE cell death, followed by regeneration within a few days, accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation.

scholarly journals SLC7A11 Reduces Laser-Induced Choroidal Neovascularization by Inhibiting RPE Ferroptosis and VEGF Production

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaohuan Zhao ◽  
Min Gao ◽  
Jian Liang ◽  
Yuhong Chen ◽  
Yimin Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cell Viability ◽  
Laser Treatment ◽  
Choroidal Neovascularization ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Rpe Cells ◽  
Age Related

In age-related macular degeneration (AMD), one of the principal sources of vascular endothelial growth factor (VEGF) is retinal pigment epithelium (RPE) cells under hypoxia or oxidative stress. Solute carrier family 7 member 11 (SLC7A11), a key component of cystine/glutamate transporter, regulates the level of cellular lipid peroxidation, and restrains ferroptosis. In our study, we assessed the role of SLC7A11 in laser-induced choroidal neovascularization (CNV) and explored the underlying mechanism. We established a mouse model of CNV to detect the expression level of SLC7A11 and VEGF during disease progression. We found the expression of the SLC7A11 protein in RPE cells peaked at 3 days after laser treatment, which was correlated with the expression of VEGF. Intraperitoneal injection of SLC7A11 inhibitor expanded the area of CNV. We examined functional proteins related to oxidative stress and Fe2+ and found laser-induced ferroptosis accompanied by increased Fe2+ content and GPX4 expression in the RPE-choroidal complex after laser treatment. We verified the expression of SLC7A11 in the ARPE19 cell line and the effects of its inhibitors on cell viability and lipid peroxidation in vitro. Application of SLC7A11 inhibitor and SLC7A11 knockdown increased the level of lipid peroxidation and reduced the cell viability of ARPE19 which can be rescued by ferroptosis inhibitors ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1). Conversely, SLC7A11 overexpression induced resistance to erastin or RSL3-induced ferroptosis. Moreover, we tested the possible regulatory transcription factor NF-E2-related factor 2 (NRF2) of SLC7A11 by Western blot. Knock-down of NRF2 decreased the expression of SLC7A11. Our study suggests that SLC7A11 plays a key role in the laser-induced CNV model by protecting RPE cells from ferroptosis. SLC7A11 provides a new therapeutic target for neovascular AMD patients.

scholarly journals Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration

2009 ◽  
Vol 297 (5) ◽  
pp. C1200-C1210 ◽  
Author(s):  
Kurt M. Bertram ◽  
Carolyn J. Baglole ◽  
Richard P. Phipps ◽  
Richard T. Libby
Keyword(s):  
Cell Death ◽  
Oxidative Damage ◽  
Macular Degeneration ◽  
Cell Size ◽  
Cigarette Smoke ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Human Rpe Cells

Cigarette smoke is the most important environmental risk factor for developing age-related macular degeneration (AMD). Damage to the retinal pigment epithelium (RPE) caused by cigarette smoke may underlie the etiology of AMD. This study investigated the molecular and cellular effects of cigarette smoke exposure on human RPE cells. ARPE-19 or primary human RPE cells were exposed to cigarette smoke extract (CSE) or hydroquinone (HQ), a component of cigarette smoke. The effect of this exposure on key aspects of RPE vitality including viability, cell size, mitochondrial membrane potential (ΔΨm), superoxide production, 4-hydroxy-2-nonenal (4-HNE), vascular endothelial growth factor (VEGF), and heme oxygenase-1 (HO-1) expression was determined. Exposure of RPE cells to CSE or HQ caused oxidative damage and apoptosis, characterized by a reduction in cell size and nuclear condensation. Evidence of oxidative damage also included increased lipid peroxidation (4-HNE) and mitochondrial superoxide production, as well as a decrease in intracellular glutathione (GSH). Exogenous administration of antioxidants (GSH and N-acetyl-cysteine) prevented oxidative damage to the RPE cells caused by CSE. Cigarette smoke also induced expression of VEGF, HO-1, and the transcription factor nuclear factor erythroid-derived 2, like 2 (NRF2). However, NRF2 was only modestly involved in CSE-induced HO-1 expression, as shown by the NRF2 small interfering RNA studies. These new findings demonstrate that cigarette smoke is a potent inducer of oxidative damage and cell death in human RPE cells. These data support the hypothesis that cigarette smoke contributes to AMD pathogenesis by causing oxidative damage and cell death to RPE cells.

scholarly journals Protective Mechanisms of the Mitochondrial-Derived Peptide Humanin in Oxidative and Endoplasmic Reticulum Stress in RPE Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Leonid Minasyan ◽  
Parameswaran G. Sreekumar ◽  
David R. Hinton ◽  
Ram Kannan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Apoptotic Cell ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Ros Generation ◽  
Rpe Cells ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss and is characterized by progressive degeneration of the retina resulting in loss of central vision. The retinal pigment epithelium (RPE) is a critical site of pathology of AMD. Mitochondria and the endoplasmic reticulum which lie in close anatomic proximity to each other are targets of oxidative stress and endoplasmic reticulum (ER) stress, respectively, and contribute to the progression of AMD. The two organelles exhibit close interactive function via various signaling mechanisms. Evidence for ER-mitochondrial crosstalk in RPE under ER stress and signaling pathways of apoptotic cell death is presented. The role of humanin (HN), a prominent member of a newly discovered family of mitochondrial-derived peptides (MDPs) expressed from an open reading frame of mitochondrial 16S rRNA, in modulation of ER and oxidative stress in RPE is discussed. HN protected RPE cells from oxidative and ER stress-induced cell death by upregulation of mitochondrial GSH, inhibition of ROS generation, and caspase 3 and 4 activation. The underlying mechanisms of ER-mitochondrial crosstalk and modulation by exogenous HN are discussed. The therapeutic use of HN and related MDPs could potentially prove to be a valuable approach for treatment of AMD.

scholarly journals Nanoceria Particles Are an Eligible Candidate to Prevent Age-Related Macular Degeneration by Inhibiting Retinal Pigment Epithelium Cell Death and Autophagy Alterations

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1617 ◽  
Author(s):  
Annamaria Tisi ◽  
Vincenzo Flati ◽  
Simona Delle Monache ◽  
Luca Lozzi ◽  
Maurizio Passacantando ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Cellular Damage ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Age Related

Retinal pigment epithelium (RPE) dysfunction and degeneration underlie the development of age-related macular degeneration (AMD), which is the leading cause of blindness worldwide. In this study, we investigated whether cerium oxide nanoparticles (CeO2-NPs or nanoceria), which are anti-oxidant agents with auto-regenerative properties, are able to preserve the RPE. On ARPE-19 cells, we found that CeO2-NPs promoted cell viability against H2O2–induced cellular damage. For the in vivo studies, we used a rat model of acute light damage (LD), which mimics many features of AMD. CeO2-NPs intravitreally injected three days before LD prevented RPE cell death and degeneration and nanoceria labelled with fluorescein were found localized in the cytoplasm of RPE cells. CeO2-NPs inhibited epithelial-mesenchymal transition of RPE cells and modulated autophagy by the down-regulation of LC3B-II and p62. Moreover, the treatment inhibited nuclear localization of LC3B. Taken together, our study demonstrates that CeO2-NPs represent an eligible candidate to counteract RPE degeneration and, therefore, a powerful therapy for AMD.

scholarly journals Effect of Thermal Stimulation on Gene Expression Related to Skeletal Muscle-derived Cell Density

2021 ◽  
pp. 73-81
Author(s):  
Masayo Nagai ◽  
Hidesuke Kaji
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cell Death ◽  
Cell Adhesion ◽  
Cell Growth ◽  
Programmed Cell Death ◽  
Mrna Expression ◽  
Thermal Stimulation ◽  
Heat Stimulation ◽  
Stimulation Of

Aims: Our previous study demonstrated favorable changes in plasma protein levels such as adiponectin by fomentation in healthy people. We also reported that the thermal stimulation caused changes of mRNA levels to prevent atherosclerosis in human skeletal muscle-derived cell (SMDC). However, cell number decreased to 74.6% by heat stimulation. In order to clarify this mechanism, we investigated whether the heat stimulation affects the levels of mRNA related to cell density or number of SMDC. Study Design: Experimental study comparing transcriptome between cells cultured at higher temperature and control cells. Place and Duration of Study: From September 2015 to March 2017, Division of Physiology and Metabolism, University of Hyogo. Methodology: SMDC was cultured at 42°C and 37°C and its gene expression was analyzed by using microarray technique. Results: Thermal stimulation of SMDC significantly altered the expression of 10 genes related to apoptosis, 1 gene related to cell division and 1 gene related to cell adhesion. mRNA expression of apoptosis promoting gene, such as THAP2 (THAP domain containing, apoptosis associated protein 2), PDCD6 (programmed cell death 6), BCL2L13 (BCL2-like 13), LOC728613 (programmed cell death 6 pseudogene), CASP4 (caspase 4), and FAS (Fas cell surface death, receptor) was up-regulated. On the other hand, PAWR (PRKC, apoptosis, WT1, regulator) was downregulated, and mRNA expression of anti-apoptotic genes, such as NOL3 (nucleolar protein 3), CIAPIN1 (cytokine-induced apoptosis inhibitor 1) and NAIF1 (nuclear apoptosis inducing factor1), was up-regulated, Gene Ontology analysis showed alterations in the expression of genes that promote apoptosis and cell growth inhibition. Pathway analysis demonstrated the pathways that promote apoptosis, stimulate cell growth and negatively or positively regulate cell adhesion. Conclusion: The present study suggested that thermal stimulation of SMDC might predominantly promote apoptosis from consistent changes in related gene expression by any analysis.

scholarly journals Solanum melongena L. Extract Protects Retinal Pigment Epithelial Cells from Blue Light-Induced Phototoxicity in In Vitro and In Vivo Models

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 359
Author(s):  
Thu Nguyen Minh Pham ◽  
Chae-Young Shin ◽  
Seo Hyun Park ◽  
Taek Hwan Lee ◽  
Hyeon Yeol Ryu ◽  
...  
Keyword(s):  
Cell Death ◽  
Blue Light ◽  
Light Exposure ◽  
Retinal Pigment ◽  
Solanum Melongena ◽  
Age Related Macular Degeneration ◽  
Retinal Layer ◽  
Therapeutic Effects ◽  
In Vivo Models

N-retinylidene-N-retinylethanolamine (A2E) accumulation in the retina is a prominent marker of retinal degenerative diseases. Blue light exposure is considered as an important factor contributing to dry age-related macular degeneration (AMD). Eggplant and its constituents have been shown to confer health benefits, but their therapeutic effects on dry AMD remain incompletely understood. In this study, we showed that an extract of Solanum melongena L. (EPX) protected A2E-laden ARPE-19 cells against blue light-induced cell death via attenuating reactive oxygen species. Transcriptomic analysis demonstrated that blue light modulated the expression of genes associated with stress response, inflammation, and cell death, and EPX suppressed the inflammatory pathway induced by blue light in A2E-laden ARPE-19 cells by inhibiting the nuclear translocation of nuclear factor kappa B and transcription of pro-inflammatory genes (CXCL8 and IL1B). The degradation of intracellular A2E was considered the major mechanism underlying the protective effect of EPX. Moreover, chlorogenic acid isolated from EPX exerted protective effects against blue light-induced cell damage in A2E-laden ARPE-19 cells. In vivo, EPX administration in BALB/c mice reduced the fundus damage and degeneration of the retinal layer in a blue light-induced retinal damage model. Collectively, our findings suggest the potential role of Solanum melongena L. extract for AMD treatment.

Quercetin-3-O-α-l-arabinopyranoside protects against retinal cell death via blue light-induced damage in human RPE cells and Balb-c mice

2018 ◽  
Vol 9 (4) ◽  
pp. 2171-2183 ◽  
Author(s):  
Jun Kim ◽  
Hong Lan Jin ◽  
Dae Sik Jang ◽  
Kwang Won Jeong ◽  
Se-Young Choung
Keyword(s):  
Cell Death ◽  
Macular Degeneration ◽  
Blue Light ◽  
Visual Loss ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Retinal Cell ◽  
Rpe Cells ◽  
Age Related ◽  
Human Rpe Cells

Age-related macular degeneration (AMD) is a chronic degenerative disease that can lead to visual loss and blindness in the elderly.

Use of Flexible Materials with a Novel Pressure Driven Equibiaxial Cell Stretching Device for Mechanical Stimulation of Single Mammalian Cells

2003 ◽  
Vol 773 ◽  
Author(s):  
James D. Kubicek ◽  
Stephanie Brelsford ◽  
Philip R. LeDuc
Keyword(s):  
Cell Fate ◽  
Mechanical Stimulation ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Single Cells ◽  
Complex Nature ◽  
Cellular Behavior ◽  
Cell Stretching ◽  
Stimulation Of ◽  
Pressure Driven

AbstractMechanical stimulation of single cells has been shown to affect cellular behavior from the molecular scale to ultimate cell fate including apoptosis and proliferation. In this, the ability to control the spatiotemporal application of force on cells through their extracellular matrix connections is critical to understand the cellular response of mechanotransduction. Here, we develop and utilize a novel pressure-driven equibiaxial cell stretching device (PECS) combined with an elastomeric material to control specifically the mechanical stimulation on single cells. Cells were cultured on silicone membranes coated with molecular matrices and then a uniform pressure was introduced to the opposite surface of the membrane to stretch single cells equibiaxially. This allowed us to apply mechanical deformation to investigate the complex nature of cell shape and structure. These results will enhance our knowledge of cellular and molecular function as well as provide insights into fields including biomechanics, tissue engineering, and drug discovery.

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