GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS

Andrew P. Voigt; Nathaniel K. Mullin; Emma M. Navratil; Miles J. Flamme-Wiese; Li-Chun Lin; Todd E. Scheetz; Ian C. Han; Edwin M. Stone; Budd A. Tucker; Robert F. Mullins

doi:10.1101/2023.06.16.544770

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GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS

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GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS

Andrew P. Voigt, Nathaniel K. Mullin, Emma M. Navratil, Miles J. Flamme-Wiese, Li-Chun Lin, Todd E. Scheetz, Ian C. Han, Edwin M. Stone, Budd A. Tucker and Robert F. Mullins

bioRxiv

Cold Spring Harbor Laboratory

06/17/2023

DOI: 10.1101/2023.06.16.544770

PMCID: PMC10312719

PMID: 37398429

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https://doi.org/10.1101/2023.06.16.544770View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Macular neovascularization is a relatively common and potentially visually devastating complication of age-related macular degeneration. In macular neovascularization, pathologic angiogenesis can originate from either the choroid or the retina, but we have limited understanding of how different cell types become dysregulated in this dynamic process. In this study, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor. We identified genes enriched within the area of macular neovascularization and used deconvolution algorithms to predict the originating cell type of these dysregulated genes. Within the area of neovascularization, endothelial cells were predicted to increase expression of genes related to Rho family GTPase signaling and integrin signaling. Likewise, VEGF and TGFB1 were identified as potential upstream regulators that could drive the observed gene expression changes produced by endothelial and retinal pigment epithelium cells in the macular neovascularization donor. These spatial gene expression profiles were compared to previous single-cell gene expression experiments in human age-related macular degeneration as well as a model of laser-induced neovascularization in mice. As a secondary aim, we also investigated spatial gene expression patterns within the macular neural retina and between the macular and peripheral choroid. We recapitulated previously described regional-specific gene expression patterns across both tissues. Overall, this study spatially analyzes gene expression across the retina, retinal pigment epithelium, and choroid in health and describes a set of candidate molecules that become dysregulated in macular neovascularization.

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Title: Subtitle: GENE EXPRESSION WITHIN A HUMAN CHOROIDAL NEOVASCULAR MEMBRANE USING SPATIAL TRANSCRIPTOMICS
Creators: Andrew P. Voigt - University of Iowa
Nathaniel K. Mullin - University of Iowa
Emma M. Navratil - University of Iowa
Miles J. Flamme-Wiese - University of Iowa
Li-Chun Lin - University of Iowa
Todd E. Scheetz - University of Iowa
Ian C. Han - University of Iowa
Edwin M. Stone - University of Iowa
Budd A. Tucker - University of Iowa
Robert F. Mullins - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2023.06.16.544770
PMID: 37398429
PMCID: PMC10312719
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 06/17/2023
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Ophthalmology and Visual Sciences
Record Identifier: 9984442225402771

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