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In-depth molecular characterization of neovascular membranes suggests a role for hyalocytes-to-myofibroblasts transdifferentiation in proliferative diabetic retinopathy

ABSTRACT: In-depth molecular characterization of neovascular membranes suggests a role for hyalocytes-to-myofibroblasts transdifferentiation in proliferative diabetic retinopathy

PROVIDER: PRJNA744210 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15051700.fastq.gz	Fastqsanger.gz
	SRR15051701.fastq.gz	Fastqsanger.gz
	SRR15051702.fastq.gz	Fastqsanger.gz
	SRR15051630.fastq.gz	Fastqsanger.gz
	SRR15051631.fastq.gz	Fastqsanger.gz

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Project description:Background: Proliferative diabetic retinopathy (PDR) is hallmarked by the formation of retinal neovascularization (RNV) membranes, which can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease. The aim of this study was to characterize the molecular and cellular features of RNV in order to unravel potential novel drug treatments for PDR. Methods: A total of 42 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Since macrophages were found to be abundant in RNV tissue, vitreal macrophages, also known as hyalocytes, were isolated from the vitreous of patients with PDR by flow cytometry, cultivated and characterized by immunhistochemistry. A bioinformatical drug repurposing approach was applied, in order to identify novel drug options for end-stage diabetic retinopathy disease. Results: The in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential drug option for future treatment of PDR. Conclusion: This study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and suggests their modulation as a novel possible clinical approach.

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In-depth molecular characterization of neovascular membranes suggests a role for hyalocytes-to-myofibroblasts transdifferentiation in proliferative diabetic retinopathy

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