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RNA-seq analyses of mouse retinal pigment epithelium cells

ABSTRACT: The retinal pigment epithelium (RPE) is a monolayer of polarized epithelial cells lying between the retina and the choroid/sclera, with a major function in supporting photoreceptor homeostasis, but the role of RPE in eye size regulation is yet to be further explored. it was recently reported that selective deletion of Low density lipoprotein receptor-related protein 2 (Lrp2) in the mouse RPE resulted in large eyes, similar to the phenotypes of Lrp2 whole eye knockout mice, suggesting that the RPE is the tissue in which LRP2 functions. Here, to investigate which downstream pathways of Srebp2 and Lrp2 are responsible for regulating eye growth, we performed RNA-seq analysis with the mouse RPE tissues. Postnatal day 0 (P0) mice were injected with AAV8-Best1-GFP/nSrebp2/ctrl sh/Lrp2 sh1/Lrp2 sh2 viruses to overexpress the constitutively active form of Srebp2 or to knockdown Lrp2 in the RPE specifically. At P14, RPE cells were carefully dissociated for RNA extraction. Via RNA-seq analysis and functional validation, we identified that Bmp2 is the target and the effector of the Srebp2-Lrp2 pathway. Overall, the present study unveils an essential role of RPE in regulating eye size via the Srebp2-Lrp2-Bmp2 signaling pathway, shedding light on the underlying mechanism of eye size control.

ORGANISM(S): Mus musculus

PROVIDER: GSE204715 | GEO | 2022/05/31

REPOSITORIES: GEO

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Proteolytic processing of LRP2 on RPE cells regulates BMP activity to control eye size and refractive error

Project description:We compare dissected ocular tissues from wild-type and lrp2-/- mutant adult zebrafish in order to examine the genetic pathways underlying the enlarged eye phenotype observed in the absence of Lrp2. ABSTRACT: Mutations in LRP2, a transmembrane receptor, cause ocular enlargement and high-myopia. LRP2 is expressed by the RPE and eye ciliary epithelia, binding many extracellular ligands, including Bmp4 and Shh. Signaling mediated by LRP2 is very context-dependent, and how multiple pathways are coordinated is unknown. Transcriptome analyses of ocular tissues revealed that controlled, sustained BMP signaling from the RPE is critical for normal eye growth and emmetropia (proper refraction). Using human iPSC-derived RPE, and zebrafish, we demonstrate that BACE sheddase-dependent LRP2 cleavage produces a soluble domain that binds BMP4, inhibiting its signaling. We propose that controlled proteolytic cleavage of LRP2 makes two ligand-binding receptor forms available: a soluble BMP trap, and a membrane-bound RPE signaling facilitator. By modulating LRP2 cleavage, cells can fine-tune and coordinate multiple signaling pathways. This data supports the concept that LRP2 acts as a homeostasis node that buffers and integrates diverse signaling to regulate emmetropic eye growth.

2018-06-01 | GSE97125 | GEO

Diurnal Gene Variation in Mouse Eye

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2015-08-09 | E-GEOD-40023 | biostudies-arrayexpress

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Project description:Proteolytic processing of LRP2 on RPE cells regulates BMP activity to control eye size and refractive error

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Next Generation Sequencing Facilitates Quantitative Analysis of a circRNA, hsa_circ_0005505 regulated Transcriptomes in breast cancer cells (MDA-MB-231 lung metastatic cells LM2)

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AR and ERG ChIP-seq in presence or absence of PRMT5

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Expression data from pooled RNA of various ocular tissues

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