Stargardt Phenotype Associated With Two <i>ELOVL4</i> Promoter Variants and <i>ELOVL4</i> Downregulation: New Possible Perspective to Etiopathogenesis?

Donato, Luigi; Scimone, Concetta; Rinaldi, Carmela; Aragona, Pasquale; Briuglia, Silvana; D’Ascola, Angela; D’Angelo, Rosalia; Sidoti, Antonina

doi:10.1167/iovs.17-22962

Cited by 42 publications

(33 citation statements)

References 70 publications

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“…In order to link these results to RP pathogenesis, the altered FASN expression induced by oxidative stress may interfere with the normal RPE morphogenesis, leading to pathological phenotype. [197][198][199][200][201][202][203] MICROVASCULAR IMPAIRMENTS The overexpression of ITGA2 could represent one of the most interesting damage caused by oxLDL, which could imply the thrombosis of retinal microcirculation, leading to cell death.…”

Section: Retinoic Acid Cycle (Rdh5 Mkv)mentioning

confidence: 99%

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis

et al. 2018

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Retinitis pigmentosa (RP) is a very heterogeneous inherited ocular disorder group characterized by progressive retinal disruption. Retinal pigment epithelium (RPE) degeneration, due to oxidative stress which arrests the metabolic support to photoreceptors, represents one of the principal causes of RP. Here, the role of oxidative stress in RP onset and progression was analyzed by a comparative whole transcriptome analysis of human RPE cells, treated with 100 µg/ml of oxLDL and untreated, at different time points. Experiment was thrice repeated and performed on Ion Proton TM sequencing system. Data analysis, including low quality reads trimming and gene expression quantification, was realized by CLC Genomics Workbench software. The whole analysis highlighted 14 clustered "macro-pathways" and many sub-pathways, classified by selection of 5271 genes showing the highest alteration of expression. Among them, 23 genes were already known to be RP causative ones (15 over-expressed and 8 down-expressed), and their enrichment and intersection analyses highlighted new 77 candidate related genes (49 over-expressed and 28 down-expressed). A final filtering analysis then highlighted 29 proposed candidate genes. This data suggests that many new genes, not yet associated with RP, could influence its etiopathogenesis.

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Section: Retinoic Acid Cycle (Rdh5 Mkv)mentioning

confidence: 99%

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis

et al. 2018

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“…Regarding the latter point, oxidative stress represents one of the major lethal mechanisms responsible for age-related RPE damages [39]. Many studies have demonstrated that accumulation of lipid deposit called lipofuscin generates reactive oxygen species through phototoxicity in RPE cells [40][41][42]. Oxidative stress triggered by photo-oxidation of bis-retinoid A2E, a lipofuscin constituent, is well known to be a progression factor of age-related macular degeneration and also in genetic macular degeneration syndromes such as Stargardt disease [43], but very little is known about A2E involvement in retinitis pigmentosa.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…ELOVL4 is an elongase that generates very long chain polyunsaturated fatty acids VLC-PUFA in the retina. Mutations in this gene have pleiotropic effects by directly altering VLC-PUFA signaling, enlarging the membrane rim curvature of photoreceptor disks and impacting on the size of ribbon synapses [62].…”

Section: Oxidative Stress Effect On Retinal Lipid Peroxidationmentioning

confidence: 99%

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

2020

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Retinal cell survival requires an equilibrium between oxygen, reactive oxygen species, and antioxidant molecules that counteract oxidative stress damage. Oxidative stress alters cell homeostasis and elicits a protective cell response, which is most relevant in photoreceptors and retinal ganglion cells, neurons with a high metabolic rate that are continuously subject to light/oxidative stress insults. We analyze how the alteration of cellular endogenous pathways for protection against oxidative stress leads to retinal dysfunction in prevalent (age-related macular degeneration, glaucoma) as well as in rare genetic visual disorders (Retinitis pigmentosa, Leber hereditary optic neuropathy). We also highlight some of the key molecular actors and discuss potential therapies using antioxidants agents, modulators of gene expression and inducers of cytoprotective signaling pathways to treat damaging oxidative stress effects and ameliorate severe phenotypic symptoms in multifactorial and rare retinal dystrophies.

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Stargardt Phenotype Associated With Two ELOVL4 Promoter Variants and ELOVL4 Downregulation: New Possible Perspective to Etiopathogenesis?

Cited by 42 publications

References 70 publications

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis

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

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

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