Chaperones and retinal disorders

Sokolov, Maxim; Yadav, Ruchika; Brooks, Celine; Artemyev, Nikolai O.

doi:10.1016/bs.apcsb.2018.09.001

Cited by 8 publications

(9 citation statements)

References 160 publications

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“…It is well known how misfolding of a huge number of proteins related to retinal survival and vision process, like rhodopsin, can result in disruptions of cellular protein homeostasis [102]. Moreover, it is high probable that the interaction between several chaperones could be altered by oxidant agents, due to activation/deactivation switches that induce certain chaperone-encoding genes or co-chaperones, and repress other ones [103]. We detected two clusters made of dysregulated lncRNAs and their interactors/host genes, involved in positive (92 interactors) and in negative regulation of cellular amide metabolism (87 interactors), respectively.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…Despite the difference in photosensitivity, the process of converting light stimuli into biochemical signals, the phototransduction cascade, is almost indistinguishable between rods and cones [3,4]. In rods, upon capture of a photon, the chromophore 11- cis retinal, which is conjugated to a rhodopsin molecule, undergoes a conformational change that isomerizes it to all- trans retinal leading to the activation of rod opsin.…”

Section: Introductionmentioning

confidence: 99%

“…The resulting hyperpolarization of the OS membrane spreads throughout the cell, eventually reaching the synaptic terminal. Here, the hyperpolarization causes closure of calcium channels and subsequently a decrease in calcium-dependent synaptic glutamate release [3,4], which activates the glutamate receptors of the bipolar cells postsynaptically, transducing the brain-bound electrical signal [6].…”

Section: Introductionmentioning

confidence: 99%

“…Defects in the conserved ciliary processes mostly manifest as syndromic ciliopathy conditions, affecting multiple organs. The most prominent ciliopathies in which the retina is affected are Bardet–Biedl syndrome (BBS), Joubert syndrome (JS), Meckel–Gruber syndrome (MKS), and Senior–Løken syndrome (SLS) [4,11]. Because PRs are highly specialized, polarized neurons, retinal ciliopathies often also occur in a nonsyndromic fashion, affecting ciliary proteins specific to rods and/or cones.…”

Section: Introductionmentioning

confidence: 99%

“…Because PRs are highly specialized, polarized neurons, retinal ciliopathies often also occur in a nonsyndromic fashion, affecting ciliary proteins specific to rods and/or cones. Based on the PR cell type affected, different IRDs can be categorized, including retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone-rod dystrophy (CRD), and achromatopsia (ACHM) [4,11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Balancing the Photoreceptor Proteome: Proteostasis Network Therapeutics for Inherited Retinal Disease

Faber

Roepman

2019

Genes

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The light sensing outer segments of photoreceptors (PRs) are renewed every ten days due to their high photoactivity, especially of the cones during daytime vision. This demands a tremendous amount of energy, as well as a high turnover of their main biosynthetic compounds, membranes, and proteins. Therefore, a refined proteostasis network (PN), regulating the protein balance, is crucial for PR viability. In many inherited retinal diseases (IRDs) this balance is disrupted leading to protein accumulation in the inner segment and eventually the death of PRs. Various studies have been focusing on therapeutically targeting the different branches of the PR PN to restore the protein balance and ultimately to treat inherited blindness. This review first describes the different branches of the PN in detail. Subsequently, insights are provided on how therapeutic compounds directed against the different PN branches might slow down or even arrest the appalling, progressive blinding conditions. These insights are supported by findings of PN modulators in other research disciplines.

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