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:10.1167/iovs.64.13.40

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Gene Expression Within a Human Choroidal Neovascular Membrane Using Spatial Transcriptomics

Journal article

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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

Investigative ophthalmology & visual science, Vol.64(13), 40

10/03/2023

DOI: 10.1167/iovs.64.13.40

PMCID: PMC10615143

PMID: 37878301

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https://doi.org/10.1167/iovs.64.13.40View

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Abstract

PurposeMacular 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. MethodsTo study how gene expression is altered in focal areas of pathology, we performed spatial RNA sequencing on a human donor eye with macular neovascularization as well as a healthy control donor. We performed differential expression to identify genes enriched within the area of macular neovascularization and used deconvolution algorithms to predict the originating cell type of these dysregulated genes. ResultsWithin the area of neovascularization, endothelial cells demonstrated increased 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 investigated regional gene expression patterns within the macular neural retina and between the macular and peripheral choroid. ConclusionsOverall, 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.

Details

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: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.64(13), 40
DOI: 10.1167/iovs.64.13.40
PMID: 37878301
PMCID: PMC10615143
NLM abbreviation: Invest Ophthalmol Vis Sci
eISSN: 1552-5783
Language: English
Date published: 10/03/2023
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: 9984500085002771

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