The Impact of miRNAs in Health and Disease of Retinal Pigment Epithelium

Intartaglia, Daniela; Giamundo, Giuliana; Conte, Iván

doi:10.3389/fcell.2020.589985

Cited by 14 publications

(8 citation statements)

References 137 publications

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“…MicroRNAs play an important role in regulating the development of AMD. [ 47 ] In vivo studies found that dysregulated miRNAs might affect AMD progression by targeting genes involved in neurodegeneration and inflammation. [ 48 ] As senescent cells cause inflammation by senescence-associated secretory phenotype, miRNAs that inhibit inflammation could be effective in the treatment of AMD.…”

Section: Discussionmentioning

confidence: 99%

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Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration

Chen

Liu

Zhang

et al. 2021

Chinese Medical Journal

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Background: Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD. Methods: The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed. Results: Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1 , CHEK1 , PSMA4 , PSMD4 , and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE. Conclusions: Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1 , CHEK1 , PSMA4 , PSMD4 , and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.

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Section: Discussionmentioning

confidence: 99%

“…MicroRNAs play an important role in regulating the development of AMD [47] . In vivo studies found that dysregulated miRNAs might affect AMD progression by targeting genes involved in neurodegeneration and inflammation [48] .…”

Section: Discussionmentioning

confidence: 99%

Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration

Chen

Liu

Zhang

et al. 2021

Chinese Medical Journal

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“…This effect is accompanied by a reduction in VEGF-induced ROS synthesis by RPE cells, neovascularization, and the EMT of RPE cells [ 357 ]. MiR-146a, activated in the RPE and choroid during cellular senescence, decreases VEGF activity in RPE cells [ 358 , 359 ]. MiR-93 and miR-302d inhibit the TGFβ signaling pathway and can be considered as a potential approach to prevent TGFβ2-mediated RPE conversion in mesenchymal transformation [ 360 ].…”

Section: The Exogenous Regulation Of Redox Homeostasis Of Rpe Cellsmentioning

confidence: 99%

Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective

Markitantova

Симирский

2023

IJMS

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The retinal pigment epithelium (RPE) performs a range of necessary functions within the neural layers of the retina and helps ensure vision. The regulation of pro-oxidative and antioxidant processes is the basis for maintaining RPE homeostasis and preventing retinal degenerative processes. Long-term stable changes in the redox balance under the influence of endogenous or exogenous factors can lead to oxidative stress (OS) and the development of a number of retinal pathologies associated with RPE dysfunction, and can eventually lead to vision loss. Reparative autophagy, ubiquitin–proteasome utilization, the repair of damaged proteins, and the maintenance of their conformational structure are important interrelated mechanisms of the endogenous defense system that protects against oxidative damage. Antioxidant protection of RPE cells is realized as a result of the activity of specific transcription factors, a large group of enzymes, chaperone proteins, etc., which form many signaling pathways in the RPE and the retina. Here, we discuss the role of the key components of the antioxidant defense system (ADS) in the cellular response of the RPE against OS. Understanding the role and interactions of OS mediators and the components of the ADS contributes to the formation of ideas about the subtle mechanisms in the regulation of RPE cellular functions and prospects for experimental approaches to restore RPE functions.

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“…It absorbs light and protects the retina from photooxidation; in addition, it is responsible for stabilizing the concentration of ions in the subretinal space to keep the photoreceptors excitable. To maintain RPE homeostasis and function, a particular molecular network is necessary, with microRNAs being indispensable components [ 94 ].…”

Section: Ocular Neurodegenerative Diseasesmentioning

confidence: 99%

Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas

Marchesi

Fahmideh

Boschi

et al. 2021

Cells

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The possible interconnection between the eye and central nervous system (CNS) has been a topic of discussion for several years just based on fact that the eye is properly considered an extension of the brain. Both organs consist of neurons and derived from a neural tube. The visual process involves photoreceptors that receive light stimulus from the external environment and send it to retinal ganglionic cells (RGC), one of the cell types of which the retina is composed. The retina, the internal visual membrane of the eye, processes the visual stimuli in electric stimuli to transfer it to the brain, through the optic nerve. Retinal chronic progressive neurodegeneration, which may occur among the elderly, can lead to different disorders of the eye such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Mainly in the elderly population, but also among younger people, such ocular pathologies are the cause of irreversible blindness or impaired, reduced vision. Typical neurodegenerative diseases of the CSN are a group of pathologies with common characteristics and etiology not fully understood; some risk factors have been identified, but they are not enough to justify all the cases observed. Furthermore, several studies have shown that also ocular disorders present characteristics of neurodegenerative diseases and, on the other hand, CNS pathologies, i.e., Alzheimer disease (AD) and Parkinson disease (PD), which are causes of morbidity and mortality worldwide, show peculiar alterations at the ocular level. The knowledge of possible correlations could help to understand the mechanisms of onset. Moreover, the underlying mechanisms of these heterogeneous disorders are still debated. This review discusses the characteristics of the ocular illnesses, focusing on the relationship between the eye and the brain. A better comprehension could help in future new therapies, thus reducing or avoiding loss of vision and improve quality of life.

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The Impact of miRNAs in Health and Disease of Retinal Pigment Epithelium

Cited by 14 publications

References 137 publications

Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration

Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration

Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective

Ocular Neurodegenerative Diseases: Interconnection between Retina and Cortical Areas

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