MiR-211 is essential for adult cone photoreceptor maintenance and visual function

Barbato, Sara; Marrocco, Elena; Intartaglia, Daniela; Pizzo, Mariateresa; Asteriti, Sabrina; Naso, Federica; Falanga, Danila; Bhat, Rajeshwari Subray; Meola, Nicola; Carissimo, Annamaria; Karali, Marianthi; Prosser, Haydn M.; Cangiano, Lorenzo; Surace, Enrico Maria; Banfi, Sandro; Conte, Iván

doi:10.1038/s41598-017-17331-z

Cited by 34 publications

(33 citation statements)

References 73 publications

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“…This pathway is likely to play a physiologically relevant role in the RPE since mice lacking miR‐211 show impaired lysosomal biogenesis and an age‐dependent accumulation of phagolysosomes containing poorly processed POS, accompanied by compromised vision. Finally, we show that pharmacological inhibition of Ezrin leads to therapeutic rescue of retinal degeneration in miR‐211 knockout (−/−) mice (Barbato et al , ). Thus, the identification of the mechanisms controlling lysosomal biogenesis in the RPE might be exploited for new therapeutic possibilities for the treatment of retinal degeneration associated with lysosomal dysfunction.…”

Section: Introductionmentioning

confidence: 71%

“…However, the functional significance of their light‐dependent expression pattern in the RPE/retina remains largely unknown. Our previous work showed that miR‐211 plays a key role in cone PR function and survival through the control of RPE/PR cell metabolism (Barbato et al , ). However, the link between the miR‐211 molecular network and cellular metabolism and its specific influence on explicit target genes responsible for the ocular phenotype is still undefined.…”

Section: Introductionmentioning

confidence: 99%

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Light‐responsive microRNA miR‐211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance

et al. 2020

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Vertebrate vision relies on the daily phagocytosis and lysosomal degradation of photoreceptor outer segments (POS) within the retinal pigment epithelium (RPE). However, how these events are controlled by light is largely unknown. Here, we show that the light-responsive miR-211 controls lysosomal biogenesis at the beginning of light-dark transitions in the RPE by targeting Ezrin, a cytoskeleton-associated protein essential for the regulation of calcium homeostasis. miR-211-mediated down-regulation of Ezrin leads to Ca 2+ influx resulting in the activation of calcineurin, which in turn activates TFEB, the master regulator of lysosomal biogenesis. Light-mediated induction of lysosomal biogenesis and function is impaired in the RPE from miR-211 À/À mice that show severely compromised vision. Pharmacological restoration of lysosomal biogenesis through Ezrin inhibition rescued the miR-211 À/À phenotype, pointing to a new therapeutic target to counteract retinal degeneration associated with lysosomal dysfunction.

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Section: Introductionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Light‐responsive microRNA miR‐211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance

et al. 2020

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“…Scotopic and photopic electrophysiological recordings were performed as described (Barbato et al, 2017). A National Instruments amplifier with a xenon Ganzfeld stimulator (CSO, Costruzione Strumenti Oftalmici, Florence, Italy) was used to record MPS-IIIA mice.…”

Section: Electrophysiological Recordingsmentioning

confidence: 99%

Retinal Degeneration in MPS-IIIA Mouse Model

Intartaglia¹,

Giamundo²,

Marrocco³

et al. 2020

Front. Cell Dev. Biol.

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Mucopolysaccharidosis type IIIA (MPS-IIIA, Sanfilippo A) is one of the most severe lysosomal storage disorder (LSD) caused by the inherited deficiency of sulfamidase, a lysosomal sulfatase enzyme involved in the stepwise degradation of heparan sulfates (HS). MPS-IIIA patients show multisystemic problems, including a strong impairment of central nervous system (CNS), mild somatic involvement, and ocular manifestations that result in significant visual impairment. Despite the CNS and somatic pathology have been well characterized, studies on visual system and function remain partially explored. Here, we characterized the retina morphology and functionality in MPS-IIIA mouse model and analyzed how the SGSH deficiency affects the autophagic flux. MPS-IIIA mice exhibited a progressive retinal dystrophy characterized by significant alterations in visual function. The photoreceptor degeneration was associated with HS accumulation and a block of autophagy pathway. These events caused a reactive microgliosis, and a development of apoptotic processes in MPS-IIIA mouse retina. Overall, this study provides the first phenotypic spectrum of retinal disorders in MPS-IIIA and significantly contributes for diagnosis, counseling, and potential therapies development.

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“…In this study, we also found that chi-miR-211 was highly expressed in cashmere goat skin in summer. MiR-211 is essential for adult cone photoreceptor maintenance [26]. These results suggested that some cells in the skin could have the potential of photosensitive, which could maintain the specific rhythm of the peripheral organs based on the environment factor (photoperiod).…”

Section: Discussionmentioning

confidence: 89%

Molecular Basis of Maintaining Circannual Rhythm in the Skin of Cashmere Goat

Liu

Gong

et al. 2020

Preprint

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The cashmere goat (Capra hircus) is famous for the fine quality cashmere wool. The cashmere is produced by secondary hair follicle that the growth shows seasonal rhythm. Thus, in this study, the skin of cashmere goat was selected as a model to illustrate the circannual rhythm of skin. The whole length skin transcriptome mixed from selected four months was obtained by PacBio single-molecule long-read sequencing (SMRT) technology. We generated 82,382 high quality non-redundant transcripts belonging to 193,310 genes, including 4,237 novel genes. Other 39 skin transcriptomes sampled from Dec. 2014 to Dec. 2015 were sequenced by Illumina Hi-Seq2500, we found 980 genes were differentially expressed. Of these genes, 403 seasonal rhythm genes (SRGs) were expressed and exhibited a seasonal pattern in skin. The results also showed that miRNAs were differentially expressed as the daylight length changed throughout a year. Some SRG genes related to the hormone secretion and eyes morphogenesis were enriched in skin. These genes gradually increased their expression level under short light, reached the peak near the summer solstice, and then began to decline. We found that the expression of Dio1 gene may be affected by the photoperiod that induces transformation from the inactive T4 to active thyroid hormone T3 in the skin and led to the difference between the skin circannual rhythm and the core circannual rhythm. Furthermore, the skin expressed eye morphogenesis-related genes and miRNAs, which suggested some cells in the skin could have the potential of light sensitivity. These results revealed that SRGs could regulate the downstream gene expression and physiological process in the skin to adapt to the season change. (SCN ) is common in fish [4, 5]. Miki Tanioka et al. first found fluctuating biomolecular clocks in the skin of mice [6]. However, subsequent studies found that both rat dermal fibroblasts [7] and human keratinocytes cultured in vitro have the same rhythm as the peripheral biological clock, and the external environment (drugs, serum) can affect the biological clock of cells cultured in vitro[8-10]. The circadian clocks of individual cells cultured in vitro are controlled by themselves, and the circadian clocks can be transmitted to the progeny cells through the process of cell division and proliferation [11]. Different types of cells in the skin have different biological clockphases. The whole biological clock in the skin is formed by the coordination of various types of cell biological clock genes [12]. Therefore, the biological clock in the skin is very complex and has memory potential, which is easily affected by light.The economic performance of livestock is mostly related to seasonal rhythm, especially the animals living in the temperate zone. Animals rely on environmental cues to judge the coming season, in order to synchronously change physiological conditions and phenotypic behavior along with environmental condition alterations, It is generally accepted that mammals perceive the light and darkness of the ...

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MiR-211 is essential for adult cone photoreceptor maintenance and visual function

Cited by 34 publications

References 73 publications

Light‐responsive microRNA miR‐211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance

Light‐responsive microRNA miR‐211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance

Retinal Degeneration in MPS-IIIA Mouse Model

Molecular Basis of Maintaining Circannual Rhythm in the Skin of Cashmere Goat

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