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Danio rerio

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

PROVIDER: PRJNA380770 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5382000.fastq.gz	Fastqsanger.gz
	SRR5382010.fastq.gz	Fastqsanger.gz
	SRR5382020.fastq.gz	Fastqsanger.gz
	SRR5382030.fastq.gz	Fastqsanger.gz
	SRR5382040.fastq.gz	Fastqsanger.gz

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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.

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RNA-seq analyses of mouse retinal pigment epithelium cells

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Project description:NEI Refractive Error Collaboration (KORA)

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Homo sapiens

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Project description:Because refractive development is governed largely by the retina, we analyzed the retinal transcriptome in chicks wearing a spectacle lens, a well-established means to induce refractive errors, to identify gene expression alterations and to develop novel mechanistic hypotheses about refractive development. One-week-old white Leghorn chicks wore a unilateral spectacle lens of + or –15 diopters for 6 hours or 3 days (n=6 for each condition). With total RNA from the retina/retinal pigment epithelium (RPE), Affymetrix Chicken GeneChips were used to compare gene expression levels between lens-wearing and contralateral control eyes. Normalized microarray signal intensities were evaluated by an analysis of variance approach. Selected differentially expressed genes were validated by qPCR in biologically independent samples.

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