Evidence map›Paper›PMID 42725908›Full record

ArticleInvestigative ophthalmology & visual science2026

Single-Nucleus RNA Sequencing Highlights Endothelial and Müller Cell ER Stress During Retinal Neovascularization in Vldlr-/- Mouse.

Angela Galdamez, Soyoung Park, William Temme, Allyssa Bradley, Ethan Stevenson, Leon Chea, Eun-Jin Lee, Jonathan H Lin

Abstract read
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Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Angela GaldamezDepartment of Ophthalmology, Stanford University, Stanford, California, United States.
Soyoung ParkDepartment of Ophthalmology, Stanford University, Stanford, California, United States.
William TemmeDepartment of Ophthalmology, Stanford University, Stanford, California, United States.
Allyssa BradleyDepartment of Ophthalmology, Stanford University, Stanford, California, United States.
Ethan StevensonDepartment of Ophthalmology, Stanford University, Stanford, California, United States.
Leon CheaDepartment of Ophthalmology, Stanford University, Stanford, California, United States.
Eun-Jin LeeDepartment of Ophthalmology, Stanford University, Stanford, California, United States.
Jonathan H LinDepartment of Ophthalmology, Stanford University, Stanford, California, United States.

Funding

Stanford Vision Research CoreP30EY026877 · NEI · STANFORD UNIVERSITY · PI Alfredo Dubra · 2017 to 2026
$8.0M
Protein Homeostasis and Proteotoxicity MechanismsR01NS088485 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LIN, JONATHAN · 2015 to 2024
$3.0M
NEI NIH HHS P30 EY026877NINDS NIH HHS R01 NS088485RRD VA IK2 RX001240
6 · The paper itself

Abstract

Purpose: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling are implicated in pathologic neovascularization, but their role in the spontaneous intraretinal/subretinal neovascularization in Vldlr-/- mice is unknown. We performed single-nucleus RNA sequencing (snRNA-seq) on adult Vldlr-/- retinas undergoing neovascularization and age-matched Vldlr+/+ control retinas. We examined differentially expressed genes in Vldlr-/- retinal cell types to identify stress signaling pathways selectively engaged in retinal cell types during pathologic neovascularization. Methods: The snRNA-seq was performed on P46 Vldlr-/- and Vldlr+/+ retinas, and differentially expressed genes and pathways associated with ER stress and UPR signaling were evaluated in retinal cell populations. KDEL and C/EBP homologous transcription factor protein (CHOP) immunostaining on retinal sections was performed to further identify retinal cell types with increased ER stress. Retinal neovascularization was evaluated by isolectin B4 (IB4) labeling of neovascular tufts and subretinal neovascularization. Retinal function was assessed by electroretinography (ERG), including oscillatory potentials. Results: IB4 staining revealed robust neovascular tufts and abnormal vessel extension into the outer retina/subretinal space. ERG and oscillatory potentials showed significantly reduced retinal function. The snRNA-seq revealed significant upregulation of ER stress/UPR signaling-associated genes selectively in endothelial cells and Müller cells. Strong KDEL and CHOP immunoreactivity was seen in IB4-positive abnormal vessels and activated Müller processes, supporting increased ER stress in these retinal cell populations. Conclusions: Endothelial cells and Müller cells show increased ER stress and UPR activation in Vldlr-/- retinas undergoing pathological neovascularization.

Indexed as

Endoplasmic Reticulum StressEndothelial CellsEpendymoglial CellsReceptors, LDLRetinal NeovascularizationAnimalsDisease Models, AnimalMiceMice, Inbred C57BLMice, KnockoutSequence Analysis, RNAUnfolded Protein ResponseReceptors, LDLVLDL receptor

Identifiers

PMID42725908
PMCPMC13576990

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.