scholarly journals Discovery of GLO1 New Related Genes and Pathways by RNA-Seq on A2E-Stressed Retinal Epithelial Cells Could Improve Knowledge on Retinitis Pigmentosa

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 416 ◽  
Author(s):  
Luigi Donato ◽  
Concetta Scimone ◽  
Simona Alibrandi ◽  
Giacomo Nicocia ◽  
Carmela Rinaldi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinitis Pigmentosa ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retrograde Transport ◽  
Antioxidant Systems ◽  
Rna Seq ◽  
Starting Point ◽  
Significant Expression

Endogenous antioxidants protect cells from reactive oxygen species (ROS)-related deleterious effects, and an imbalance in the oxidant/antioxidant systems generates oxidative stress. Glyoxalase 1 (GLO1) is a ubiquitous cellular enzyme involved in detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis whose excess can produce oxidative stress. In retinitis pigmentosa, one of the most diffuse cause of blindness, oxidative damage leads to photoreceptor death. To clarify the role of GLO1 in retinitis pigmentosa onset and progression, we treated human retinal pigment epithelium cells by the oxidant agent A2E. Transcriptome profiles between treated and untreated cells were performed by RNA-Seq, considering two time points (3 and 6 h), after the basal one. The exposure to A2E highlighted significant expression differences and splicing events in 370 GLO1 first-neighbor genes, and 23 of them emerged from pathway clustered analysis as main candidates to be associated with retinitis pigmentosa. Such a hypothesis was corroborated by the involvement of previously analyzed genes in specific cellular activities related to oxidative stress, such as glyoxylate and dicarboxylate metabolism, glycolysis, axo-dendritic transport, lipoprotein activity and metabolism, SUMOylation and retrograde transport at the trans-Golgi network. Our findings could be the starting point to explore unclear molecular mechanisms involved in retinitis pigmentosa etiopathogenesis.

scholarly journals PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jia He ◽  
Chongde Long ◽  
Zixin Huang ◽  
Xin Zhou ◽  
Xielan Kuang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Age Related ◽  
Induced Apoptosis

Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α(one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.

scholarly journals Effects of A2E-Induced Oxidative Stress on Retinal Epithelial Cells: New Insights on Differential Gene Response and Retinal Dystrophies

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 307 ◽  
Author(s):  
Luigi Donato ◽  
Rosalia D’Angelo ◽  
Simona Alibrandi ◽  
Carmela Rinaldi ◽  
Antonina Sidoti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Genetic Diseases ◽  
Age Related Macular Degeneration ◽  
Retinal Cell ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Age Related

Oxidative stress represents one of the principal inductors of lifestyle-related and genetic diseases. Among them, inherited retinal dystrophies, such as age-related macular degeneration and retinitis pigmentosa, are well known to be susceptible to oxidative stress. To better understand how high reactive oxygen species levels may be involved in retinal dystrophies onset and progression, we performed a whole RNA-Seq experiment. It consisted of a comparison of transcriptomes’ profiles among human retinal pigment epithelium cells exposed to the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering two time points (3h and 6h) after the basal one. The treatment with A2E determined relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration. We found 10 different clusters of pathways involving differentially expressed and differentially alternative spliced genes and highlighted the sub- pathways which could depict a more detailed scenario determined by the oxidative-stress-induced condition. In particular, regulation and/or alterations of angiogenesis, extracellular matrix integrity, isoprenoid-mediated reactions, physiological or pathological autophagy, cell-death induction and retinal cell rescue represented the most dysregulated pathways. Our results could represent an important step towards discovery of unclear molecular mechanisms linking oxidative stress and etiopathogenesis of retinal dystrophies.

scholarly journals Transcriptome Analyses of lncRNAs in A2E-Stressed Retinal Epithelial Cells Unveil Advanced Links between Metabolic Impairments Related to Oxidative Stress and Retinitis Pigmentosa

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 318 ◽  
Author(s):  
Luigi Donato ◽  
Concetta Scimone ◽  
Simona Alibrandi ◽  
Carmela Rinaldi ◽  
Antonina Sidoti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinitis Pigmentosa ◽  
Cellular Response ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Differentially Expressed ◽  
Retinal Cell ◽  
Relevant Role ◽  
Human Disorders ◽  
Epithelium Cells

Long non-coding RNAs (lncRNAs) are untranslated transcripts which regulate many biological processes. Changes in lncRNA expression pattern are well-known related to various human disorders, such as ocular diseases. Among them, retinitis pigmentosa, one of the most heterogeneous inherited disorder, is strictly related to oxidative stress. However, little is known about regulative aspects able to link oxidative stress to etiopathogenesis of retinitis. Thus, we realized a total RNA-Seq experiment, analyzing human retinal pigment epithelium cells treated by the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering three independent experimental groups (untreated control cells, cells treated for 3 h and cells treated for 6 h). Differentially expressed lncRNAs were filtered out, explored with specific tools and databases, and finally subjected to pathway analysis. We detected 3,3’-overlapping ncRNAs, 107 antisense, 24 sense-intronic, four sense-overlapping and 227 lincRNAs very differentially expressed throughout all considered time points. Analyzed lncRNAs could be involved in several biochemical pathways related to compromised response to oxidative stress, carbohydrate and lipid metabolism impairment, melanin biosynthetic process alteration, deficiency in cellular response to amino acid starvation, unbalanced regulation of cofactor metabolic process, all leading to retinal cell death. The explored lncRNAs could play a relevant role in retinitis pigmentosa etiopathogenesis, and seem to be the ideal candidate for novel molecular markers and therapeutic strategies.

scholarly journals Analysis of saponins detoxification genes in Ilyonectria mors-panacis G3B inducing root rot of Panax notoginseng by RNA-Seq

2021 ◽  
Author(s):  
Guohong Zeng ◽  
Jin Li ◽  
Yuxiu Ma ◽  
Qian Pu ◽  
Tian Xiao ◽  
...  
Keyword(s):  
Root Rot ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
Panax Notoginseng ◽  
Glycoside Hydrolases ◽  
Rna Seq ◽  
Host Interaction ◽  
Excellent Starting Point ◽  
Starting Point ◽  
Genes Encoding

AbstractSaponins are kinds of antifungal compounds produced by Panax notoginseng to resist invasion by pathogens. Ilyonectria mors-panacis G3B was the dominant pathogen inducing root rot of P. notoginseng, and the abilities to detoxify saponins were the key to infect P. notoginseng successfully. To research the molecular mechanisms of detoxifying saponins in I. mors-panacis G3B, we used high-throughput RNA-Seq to identify 557 and 1519 differential expression genes (DEGs) in I. mors-panacis G3B with saponins treatments for 4H (Hours) and 12H (Hours) compared with no saponins treatments, respectively. Among these DEGs, we found 93 genes which were simultaneously highly expressed in I. mors-panacis G3B with saponins treatments for 4H and 12H, they mainly belong to genes encoding transporters, glycoside hydrolases, oxidation–reduction enzymes, transcription factors and so on. In addition, there were 21 putative PHI (Pathogen–Host Interaction) genes out of those 93 up-regulated genes. In this report, we analyzed virulence-associated genes in I. mors-panacis G3B which may be related to detoxifying saponins to infect P. notoginseng successfully. They provided an excellent starting point for in-depth study on pathogenicity of I. mors-panacis G3B and developed appropriate root rot disease management strategies in the future.

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.

scholarly journals CIB2 regulates mTORC1 signaling and is essential for autophagy and visual function

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Saumil Sethna ◽  
Patrick A. Scott ◽  
Arnaud P. J. Giese ◽  
Todd Duncan ◽  
Xiaoying Jian ◽  
...  
Keyword(s):  
Visual Function ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Negative Regulator ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Mtorc1 Signaling ◽  
Marked Accumulation

AbstractAge-related macular degeneration (AMD) is a multifactorial neurodegenerative disorder. Although molecular mechanisms remain elusive, deficits in autophagy have been associated with AMD. Here we show that deficiency of calcium and integrin binding protein 2 (CIB2) in mice, leads to age-related pathologies, including sub-retinal pigment epithelium (RPE) deposits, marked accumulation of drusen markers APOE, C3, Aβ, and esterified cholesterol, and impaired visual function, which can be rescued using exogenous retinoids. Cib2 mutant mice exhibit reduced lysosomal capacity and autophagic clearance, and increased mTORC1 signaling—a negative regulator of autophagy. We observe concordant molecular deficits in dry-AMD RPE/choroid post-mortem human tissues. Mechanistically, CIB2 negatively regulates mTORC1 by preferentially binding to ‘nucleotide empty’ or inactive GDP-loaded Rheb. Upregulated mTORC1 signaling has been implicated in lymphangioleiomyomatosis (LAM) cancer. Over-expressing CIB2 in LAM patient-derived fibroblasts downregulates hyperactive mTORC1 signaling. Thus, our findings have significant implications for treatment of AMD and other mTORC1 hyperactivity-associated disorders.

scholarly journals USH2A-Related Retinitis Pigmentosa: Staging of Disease Severity and Morpho-Functional Studies

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 213
Author(s):  
Benedetto Falsini ◽  
Giorgio Placidi ◽  
Elisa De Siena ◽  
Maria Cristina Savastano ◽  
Angelo Maria Minnella ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Usher Syndrome ◽  
Collaborative Study ◽  
Staging System ◽  
International Standards ◽  
Full Field ◽  
Functional Studies ◽  
Cumulative Score

Usher syndrome type 2A (USH2A) is a genetic disease characterized by bilateral neuro-sensory hypoacusia and retinitis pigmentosa (RP). While several methods, including electroretinogram (ERG), describe retinal function in USH2A patients, structural alterations can be assessed by optical coherence tomography (OCT). According to a recent collaborative study, RP can be staged considering visual acuity, visual field area and ellipsoid zone (EZ) width. The aim of this study was to retrospectively determine RP stage in a cohort of patients with USH2A gene variants and to correlate the results with age, as well as additional functional and morphological parameters. In 26 patients with established USH2A genotype, RP was staged according to recent international standards. The cumulative staging score was correlated with patients’ age, amplitude of full-field and focal flicker ERGs, and the OCT-measured area of sub-Retinal Pigment Epithelium (RPE) illumination (SRI). RP cumulative score (CS) was positively correlated (r = 0.6) with age. CS was also negatively correlated (rho = −0.7) with log10 ERG amplitudes and positively correlated (r = 0.5) with SRI. In USH2A patients, RP severity score is correlated with age and additional morpho-functional parameters not included in the international staging system and can reliably predict their abnormality at different stages of disease.

Sign in / Sign up

Export Citation Format

Share Document