scholarly journals Antioxidant and Cytoprotective Potential of Erythropoietin in Mitigating Oxidative Stress-Induced Changes in the Retinal Pigment Epithelium

2021 ◽  
Author(s):  
Manas R. Biswal ◽  
Zhaoyao Wang ◽  
Ryan J. Paulson ◽  
Rukshana R. Uddin ◽  
Yao Tong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Protective Enzyme ◽  
Serotype 1 ◽  
The Right ◽  
Induced Changes ◽  
And Control

Erythropoietin (EPO) protects cells by inhibiting apoptosis, oxidative stress and inflammation in several models of retinal degeneration. In this study, we demonstrate the effects of recombinant Adeno Associated Virus (AAV) vector-mediated delivery of a modified form of erythropoietin (EPO-R76E) in an established mouse model of dry-AMD in which retinal degeneration is induced by RPE oxidative stress. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/Choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific exogenous protein expression. Retinal degeneration was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the progressive retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress as seen in this mouse model.

scholarly journals Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from Oxidative Stress in the Retinal Pigment Epithelium

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 842
Author(s):  
Manas R. Biswal ◽  
Zhaoyao Wang ◽  
Ryan J. Paulson ◽  
Rukshana R. Uddin ◽  
Yao Tong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Protective Enzyme ◽  
Age Related ◽  
Serotype 1 ◽  
The Right

Erythropoietin (EPO) plays an important role in erythropoiesis by its action in blocking apoptosis of progenitor cells and protects both photoreceptors and retinal ganglion cells from induced or inherited degeneration. A modified form of EPO, EPO-R76E has attenuated erythropoietic activity but is effective in inhibiting apoptosis, oxidative stress, and inflammation in several models of retinal degeneration. In this study, we used recombinant Adeno Associated Virus (AAV) to provide long-term sustained delivery of EPO-R76E and demonstrated its effects in a mouse model of dry-AMD in which retinal degeneration is induced by oxidative stress in the retinal pigment epithelial (RPE) cells. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE/choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific EPO expression. Retinal function was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress, which is implicated as a potential cause of Age-Related Macular Degeneration.

Recessive Familial Spastic Paraplegia with Retinal Degeneration

1974 ◽  
Vol 23 (S1) ◽  
pp. 249-252 ◽  
Author(s):  
W. Macrae ◽  
J. Stieffel ◽  
A.B. Todorov
Keyword(s):  
Retinal Pigment Epithelium ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Spastic Paraplegia ◽  
Reticular Pattern ◽  
Ocular Symptoms ◽  
Window Effect ◽  
Familial Spastic Paraplegia ◽  
The Right

A family is described in which spastic paraplegia and retinal degeneration were observed in 5 out of 11 sibs in one generation. All affected members of this family had the onset of bilateral ocular symptoms during the fourth to fifth decade. Visual impairment was slowly progressive and ranged from 20/25 to 20/100.There was a macular and perimacular speckling with small, irregular, discrete spots and central pigment proliferation, at the level of the pigment epithelium. Fluorescein angiography revealed patches of proliferating retinal pigment epithelium blocking transmission of fluorescein, surrounded by a larger area of disruption of the retinal pigment epithelium giving a “window-effect” choroidal pattern. The right macula showed a nonspecific, nonfluorescent, reticular pattern.The most likely explanation of the ocular findings was a retinal degeneration involving the retinal pigment epithelium and/or the chorio-capillaries. Extensive laboratory work was negative.

scholarly journals A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration

2019 ◽  
Vol 20 (19) ◽  
pp. 4807 ◽  
Author(s):  
Feng Su ◽  
Christine Spee ◽  
Eduardo Araujo ◽  
Eric Barron ◽  
Mo Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Disease ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Mimetic Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration.

scholarly journals Mitophagy in the Retinal Pigment Epithelium of Dry Age-Related Macular Degeneration Investigated in the NFE2L2/PGC-1α-/- Mouse Model

2020 ◽  
Vol 21 (6) ◽  
pp. 1976 ◽  
Author(s):  
Iswariyaraja Sridevi Gurubaran ◽  
Johanna Viiri ◽  
Ali Koskela ◽  
Juha M.T. Hyttinen ◽  
Jussi J. Paterno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Double Knockout ◽  
Rpe Cells ◽  
Age Related

Increased oxidative stress and mitochondrial damage are observed in protein aggregation diseases, such as age-related macular degeneration (AMD). We have recently reported elevated levels of oxidative stress markers, damaged mitochondria, accumulating lysosomal lipofuscin and extracellular drusen-like structures in the retinal pigment epithelial cells (RPE) of the dry AMD-resembling NFE2L2/PGC1α double knockout (dKO) mouse model. Here, we provide evidence of a disturbance in the autolysosomal machinery handling mitochondrial clearance in the RPE cells of one-year-old NFE2L2/PGC1α-deficient mice. Confocal immunohistochemical analysis revealed an upregulation of autophagosome marker microtubule-associated proteins 1A/1B light chain 3B (LC3B) as well as numerous mitophagy markers, such as PTE-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase (PARKIN) together with damaged mitochondria. However, we detected no evidence of increased autolysosome formation in transmission electron micrographs or of colocalization of lysosomal marker LAMP2 (lysosome-associated membrane protein 2) and the mitochondrial marker ATP synthase β in confocal micrographs. Interestingly, we observed an upregulation of late autolysosomal fusion Ras-related protein (Rab7) in the perinuclear space of RPE cells together with autofluorescence aggregates. Our results reveal that there is at least a relative decrease of mitophagy in the RPE cells of NFE2L2/PGC1α dKO mice. This further supports the hypothesis that mitophagy is a putative therapy target in AMD-like pathology.

scholarly journals Reintroduction of DJ-1 in Müller Cells Inhibits Retinal Degeneration in the DJ-1 Deficient Retina

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1862
Author(s):  
Naouel Gharbi ◽  
Dagne Røise ◽  
Jorunn-Elise Førre ◽  
Amanda J. Edson ◽  
Helena A. Hushagen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Light Exposure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Müller Cells ◽  
Müller Cell ◽  
Muller Cells ◽  
Age Dependent ◽  
Muller Cell

The eye is continuously under oxidative stress due to high metabolic activity and reactive oxygen species generated by daily light exposure. The redox-sensitive protein DJ-1 has proven to be essential in order to protect retina and retinal pigment epithelium (RPE) from oxidative-stress-induced degeneration. Here, we analyzed the specific role of Müller cell DJ-1 in the adult zebrafish retina by re-establishing Müller-cell-specific DJ-1 expression in a DJ-1 knockout retina. Loss of DJ-1 resulted in an age-dependent retinal degeneration, including loss of cells in the ganglion cell layer, retinal thinning, photoreceptor disorganization and RPE cell dysfunction. The degenerative phenotype induced by the absence of DJ-1 was inhibited by solely expressing DJ-1 in Müller cells. The protective effect was dependent upon the cysteine-106 residue of DJ-1, which has been shown to be an oxidative sensor of DJ-1. In a label-free proteomics analysis of isolated retinas, we identified proteins differentially expressed after DJ-1 knockout, but with restored levels after Müller cell DJ-1 re-insertion. Our data show that Müller cell DJ-1 has a major role in protecting the retina from age-dependent oxidative stress.

scholarly journals Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0203816 ◽  
Author(s):  
Manas R. Biswal ◽  
Bradley D. Justis ◽  
Pingyang Han ◽  
Hong Li ◽  
Dennis Gierhart ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelium ◽  
Mouse Model ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Mitochondrial Oxidative Stress

scholarly journals Protection of Kaempferol on Oxidative Stress-Induced Retinal Pigment Epithelial Cell Damage

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Weiwei Du ◽  
Yuanlong An ◽  
Xiangdong He ◽  
Donglei Zhang ◽  
Wei He
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Cell Damage ◽  
Retinal Pigment Epithelial Cell ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Sodium Iodate ◽  
Rpe Cells ◽  
Age Related

The protection of retinal pigment epithelium (RPE) injury plays an important role in the prevention of or in delaying the pathological progress of retinal degeneration diseases, like age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa. Oxidative stress has been identified as a major inducer of RPE injury, which eventually could lead to a loss of vision. Kaempferol is a natural flavonoid widely distributed in many edible plants, fruits, and traditional medicines and has been reported to have antioxidant, anti-inflammatory, anticancer, and antimicrobial activities. The present study demonstrates that the total antioxidant capacity of kaempferol is approximately two times stronger than that of lutein which is also a natural antioxidant that is widely used in the prevention or treatment of AMD. Our data indicates that kaempferol protects human RPE cells (ARPE-19) from hydrogen peroxide- (H2O2-) induced oxidative cell damage and apoptosis through the signaling pathways involving Bax/Bcl-2 and caspase-3 molecules proofed by real-time PCR and Western blot results. Kaempferol also inhibits the upregulated vascular endothelial growth factor (VEGF) mRNA expression levels induced by H2O2 in ARPE-19 cells and affects the oxidation and antioxidant imbalanced system in ARPE-19 cells treated by H2O2 through the regulations of both the activities of reactive oxygen species (ROS) and superoxide dismutase (SOD). Furthermore, our in vivo experimental results show that in sodium iodate-induced retinal degeneration rat model, kaempferol could protect sodium iodate-induced pathological changes of retina tissue and retinal cells apoptosis as well as the upregulated VEGF protein expression in RPE cells. In summary, these novel findings demonstrate that kaempferol could protect oxidative stressed-human RPE cell damage through its antioxidant activity and antiapoptosis function, suggesting that kaempferol has a potential role in the prevention and therapeutic treatment of AMD or other retinal diseases mediated by oxidative stress.

scholarly journals The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 64
Author(s):  
Annamaria Tisi ◽  
Marco Feligioni ◽  
Maurizio Passacantando ◽  
Marco Ciancaglini ◽  
Rita Maccarone
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Functional Changes ◽  
Beneficial Effects ◽  
Age Related ◽  
The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

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