scholarly journals Anti-VEGF Drugs Influence Epigenetic Regulation and AMD-Specific Molecular Markers in ARPE-19 Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 878
Author(s):  
Mohamed A. Hamid ◽  
M. Tarek Moustafa ◽  
Sonali Nashine ◽  
Rodrigo Donato Costa ◽  
Kevin Schneider ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Deacetylase ◽  
Retinal Pigment Epithelial ◽  
Caspase 3 ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Caspase 9 ◽  
Hdac Activity ◽  
Pigment Epithelial ◽  
Anti Vegf

Our study assesses the effects of anti-VEGF (Vascular Endothelial Growth Factor) drugs and Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC) activity, on cultured ARPE-19 (Adult Retinal Pigment Epithelial-19) cells that are immortalized human retinal pigment epithelial cells. ARPE-19 cells were treated with the following anti-VEGF drugs: aflibercept, ranibizumab, or bevacizumab at 1× and 2× concentrations of the clinical intravitreal dose (12.5 μL/mL and 25 μL/mL, respectively) and analyzed for transcription profiles of genes associated with the pathogenesis age-related macular degeneration (AMD). HDAC activity was measured using the Fluorometric Histone Deacetylase assay. TSA downregulated HIF-1α and IL-1β genes, and upregulated BCL2L13, CASPASE-9, and IL-18 genes. TSA alone or bevacizumab plus TSA showed a significant reduction of HDAC activity compared to untreated ARPE-19 cells. Bevacizumab alone did not significantly alter HDAC activity, but increased gene expression of SOD2, BCL2L13, CASPASE-3, and IL-18 and caused downregulation of HIF-1α and IL-18. Combination of bevacizumab plus TSA increased gene expression of SOD2, HIF-1α, GPX3A, BCL2L13, and CASPASE-3, and reduced CASPASE-9 and IL-β. In conclusion, we demonstrated that anti-VEGF drugs can: (1) alter expression of genes involved in oxidative stress (GPX3A and SOD2), inflammation (IL-18 and IL-1β) and apoptosis (BCL2L13, CASPASE-3, and CASPASE-9), and (2) TSA-induced deacetylation altered transcription for angiogenesis (HIF-1α), apoptosis, and inflammation genes.

scholarly journals Sulforaphane Enhances the Ability of Human Retinal Pigment Epithelial Cell against Oxidative Stress, and Its Effect on Gene Expression Profile Evaluated by Microarray Analysis

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Liang Ye ◽  
Ting Yu ◽  
Yanqun Li ◽  
Bingni Chen ◽  
Jinshun Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Microarray Analysis ◽  
Retinal Pigment Epithelial ◽  
Nuclear Translocation ◽  
Retinal Pigment ◽  
Regulation Of Gene Expression ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Pigment Epithelial

To gain further insights into the molecular basis of Sulforaphane (SF) mediated retinal pigment epithelial (RPE) 19 cell against oxidative stress, we investigated the effects of SF on the regulation of gene expression on a global scale and tested whether SF can endow RPE cells with the ability to resist apoptosis. The data revealed that after exposure to H2O2, RPE 19 cell viability was increased in the cells pretreated with SF compared to the cell not treated with SF. Microarray analysis revealed significant changes in the expression of 69 genes in RPE 19 cells after 6 hours of SF treatment. Based on the functional relevance, eight of the SF-responsive genes, that belong to antioxidant redox system, and inflammatory responsive factors were validated. The up-regulating translation of thioredoxin-1 (Trx1) and the nuclear translocation of Nuclear factor-like2 (Nrf2) were demonstrated by immunoblot analysis in SF treated RPE cells. Our data indicate that SF increases the ability of RPE 19 cell against oxidative stress through up-regulating antioxidative enzymes and down-regulating inflammatory mediators and chemokines. The results suggest that the antioxidant, SF, may be a valuable supplement for preventing and retarding the development of Age Related Macular Degeneration.

scholarly journals Bilateral Refractive Changes in Vascularized Pigment Epithelial Detachment Treated by Anti-VEGF Therapy

2015 ◽  
Vol 6 (3) ◽  
pp. 458-461
Author(s):  
Joel Hanhart ◽  
Itay Chowers
Keyword(s):  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Response To Treatment ◽  
Pigment Epithelial Detachment ◽  
Retinal Pigment Epithelial Detachment ◽  
Pigment Epithelial ◽  
Intraocular Injection ◽  
Anti Vegf ◽  
Age Related

We report the case of a patient bilaterally treated with anti-VEGF compounds for bilateral massive vascularized retinal pigment epithelial detachment (PED). During the years prior to treatment, PED growth was accompanied by gradual hypermetropization. After right intraocular injection of bevacizumab followed by three bilateral aflibercept injections, the PED flattened resulting in a rapid relative myopization. This case illustrates ocular refractive properties associated with PED and its response to treatment. This case also highlights the importance of assessing refraction in age-related macular degeneration patients experiencing substantial PED amplitude changes.

Retinal Pigment Epithelial Tear after Ranibizumab Therapy for Subfoveal Fibrovascular Pigment Epithelial Detachment

2007 ◽  
Vol 17 (4) ◽  
pp. 674-676 ◽  
Author(s):  
C.K. Chan ◽  
S.G. Lin
Keyword(s):  
Case Report ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Fundus Photography ◽  
Unusual Complication ◽  
Pigment Epithelial Detachment ◽  
Pigment Epithelial ◽  
Anti Vegf ◽  
Rpe Tear

Purpose To describe the unusual complication of retinal pigment epithelial (RPE) tear after intravitreal ranibizumab (Lucentis®) for subfoveal fibrovascular pigment epithelial detachment (PED) and its effective management. Methods Chart review for case report of RPE tear after ranibizumab. Results An inferior RPE tear was documented by fluorescein angiography, fundus photography, and optical coherence tomography (OCT) 1 month after receiving repeat ranibizumab injection in the right eye of a patient with bilateral subfoveal fibrovascular PED. He had undergone multiple bevacizumab followed by ranibizumab injections for neovascular age-related macular degeneration (AMD) in both eyes, starting 6 months previously. Subsequent antivascular endothelial growth factor (VEGF) therapy improved vision of right eye from 20/200 to 20/40, despite RPE tear. Conclusions RPE tear may form after anti-VEGF therapy, including ranibizumab injection. Further anti-VEGF therapy may preserve or improve vision. To the authors' knowledge, this is first case report of effective suppression of neovascular activity with bevacizumab after an RPE tear following ranibizumab therapy.

scholarly journals Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration

Oncotarget ◽  
2016 ◽  
Vol 7 (8) ◽  
pp. 8532-8545 ◽  
Author(s):  
Ahmed S. Ibrahim ◽  
Suchreet Mander ◽  
Khaled A. Hussein ◽  
Nehal M. Elsherbiny ◽  
Sylvia B. Smith ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Structure And Function ◽  
Age Related Macular Degeneration ◽  
Pigment Epithelial ◽  
Age Related ◽  
Epithelial Structure ◽  
And Function
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