Disruption of miR-18a Alters Proliferation, Photoreceptor Replacement Kinetics, Inflammatory Signaling, and Microglia/Macrophage Numbers During Retinal Regeneration in Zebrafish

Magner, Evin; Sandoval-Sanchez, Pamela; Kramer, Ashley C.; Thummel, Ryan; Hitchcock, Peter F.; Taylor, Scott M.

doi:10.1007/s12035-022-02783-w

Cited by 8 publications

(8 citation statements)

References 79 publications

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“…Interestingly, recent investigations have underscored the critical role of inflammation in the reprogramming of multipotent retinal stem cells during regenerative processes. Prolonged inflammatory responses mediated by retinal microglia/macrophages have been shown to impact the proliferation of RPCs and impede the induction of photoreceptors’ regenerative response [ 46 , 47 , 48 ]. This implies that a nuanced inflammatory milieu is conducive to cellular reprogramming and cell cycle re-entry, whereas excessive inflammation may exert inhibitory effects on retinal regeneration [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…This implies that a nuanced inflammatory milieu is conducive to cellular reprogramming and cell cycle re-entry, whereas excessive inflammation may exert inhibitory effects on retinal regeneration [ 49 ]. Intriguingly, mitigation of excessive inflammation through dexamethasone intervention has demonstrated in vivo restoration of RPCs regenerative phenotypes [ 46 ]. Likewise, in vitro treatment with dexamethasone has also exhibited an augmentation in the self-renewal and proliferation of CE neurospheres [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

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Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells

Dalmaso,

Silva-Junior,

Jancar

et al. 2024

IJMS

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The retina is a central nervous tissue essential to visual perception and highly susceptible to environmental damage. Lower vertebrate retinas activate intrinsic regeneration mechanisms in response to retinal injury regulated by a specialized population of progenitor cells. The mammalian retina does not have populations of progenitor/stem cells available to activate regeneration, but contains a subpopulation of differentiated cells that can be reprogrammed into retinal stem cells, the ciliary epithelium (CE) cells. Despite the regenerative potential, stem cells derived from CE exhibit limited reprogramming capacity probably associated with the expression of intrinsic regulatory mechanisms. Platelet-activating factor (PAF) is a lipid mediator widely expressed in many cells and plays an important role in stem cell proliferation and differentiation. During mammalian development, PAF receptor signaling showed important effects on retinal progenitors’ cell cycle regulation and neuronal differentiation that need to be further investigated. In this study, our findings suggested a dynamic role for PAF receptor signaling in CE cells, impacting stem cell characteristics and neurosphere formation. We showed that PAF receptors and PAF-related enzymes are downregulated in retinal progenitor/stem cells derived from PE cells. Blocking PAFR activity using antagonists increased the expression of specific progenitor markers, revealing potential implications for retinal tissue development and maintenance.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells

Dalmaso,

Silva-Junior,

Jancar

et al. 2024

IJMS

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“…Several of the circRNA-associated miRNAs are expressed in the brain, with relatively defined roles in brain development (miR-18a, miR-18b [ 25 , 26 ], miR-30 [ 27 , 28 ], miR-592 [ 29 , 30 ]) or adult brain (miR-18a [ 31 , 32 ], miR-149 [ 33 , 34 , 35 ], miR-30 [ 36 , 37 ], miR-21 [ 28 , 38 ], miR-592 [ 39 ]. Some of these were investigated in the field of dementias and neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

Manzini

Rivabene

Crestini

et al. 2022

IJMS

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The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD.

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“…However, after mutation of miR-18a in the retina, retinal microglia are activated, the expression of inflammatory genes is upregulated, and the conversion of Müller cells into neurones is inhibited. 34 …”

Section: Roles Of Mirna In Müller Cells On Retinal Regenerationmentioning

confidence: 99%

New insights on the role of microRNAs in retinal Müller glial cell function

Jiang,

He,

Liu

et al. 2023

Br J Ophthalmol

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MicroRNAs belong to the family of non-coding RNAs that participate in cell proliferation, cell death and development. The Müller glial cells are the inherent and specific neuroglia cells in the retinal organisation and play significant roles in retinal neuroprotection, organisational maintenance, inflammation and immunity, regeneration, and the occurrence and development of retinal diseases. However, only a few studies report the underlying mechanism of how miRNAs drive the function of Müller glial cells in the development of retinal diseases. This review aims to summarise the roles of miRNAs in retinal Müller glial cell function, including gliogenesis, inflammation and immunity, regeneration, the development of retinal diseases, and retinal development. This review may point out a novel miRNA-based insight into retinal repair and regeneration. MiRNAs in Müller glial cells may be considered a diagnostic and therapeutic target in the process of retinal repair and regeneration.

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Disruption of miR-18a Alters Proliferation, Photoreceptor Replacement Kinetics, Inflammatory Signaling, and Microglia/Macrophage Numbers During Retinal Regeneration in Zebrafish

Cited by 8 publications

References 79 publications

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells

Platelet-Activating Factor Receptor (PAFR) Regulates Retinal Progenitor/Stem Cells Profile in Ciliary Epithelium Cells

A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls

New insights on the role of microRNAs in retinal Müller glial cell function

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