ArticleImmunity2022
Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma.
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Article in Immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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93citing papers in PubMed
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93 citing papers in PubMed, 116 citations in OpenAlex.
- Immunological drivers of oxidative stress in glaucoma: implications for antioxidant therapy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Galectin-3 is elevated in Müller glia in human glaucomatous eyes and ocular hypertensive rat eyes and associated with phagocytosing states.Acta neuropathologica communications · 2026Article
- Reprogramming Glial Cell Metabolism via a tRNA Fragment Preserves Vision in Retinal Neurodegeneration.MedComm · 2026Article
- Genetic context alters central nervous system compartment dependent responses to lipopolysaccharide.bioRxiv : the preprint server for biology · 2026Article
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- A dual-responsive CO-releasing nanogel ameliorates retinal ischemia-reperfusion injury by restoring mitochondrial homeostasis and attenuating cGAS-STING pathway activation.Materials today. Bio · 2026Article
- Glaucoma and Autoimmunity: Immunopathogenic Mechanisms and Emerging Immunomodulatory Therapies.Biomedicines · 2026Review
- The role of prostanoids in the retina and optic nerve in health and disease.Progress in retinal and eye research · 2026Review
- Age-Related Neurovascular Dysfunction in the Retina and Potential Pathogenic Mechanisms.Investigative ophthalmology & visual science · 2026Review
- Microglial polarization in retinal neovascularization: Friend or foe?Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- The utility of aqueous and serum apolipoprotein E and galectin-3 as biomarkers of neuroinflammation in glaucoma.Scientific reports · 2026Article
- Targeting Apolipoprotein E4 rescues photoreceptor degeneration by inhibiting the disease-associated microglia activation in experimental retinal detachment.Journal of neuroinflammation · 2026Article
- Optic Nerve Head Spatial Transcriptomic Change in Nonhuman Primate Early Experimental Glaucoma.Investigative ophthalmology & visual science · 2026Article
- Association of High-Density Lipoprotein Cholesterol with Macular Structure in Nonglaucomatous Individuals.Ophthalmology science · 2026Article
- Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026Review
- St6gal1-mediated sialylation protects retinal ganglion cells by restraining microglial phagocytosis.Journal of neuroinflammation · 2026Article
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Cell-intrinsic vulnerability and immune activation cooperate to drive degeneration in a mitochondrial complex I deficiency model of optic neuropathy.Journal of neuroinflammation · 2026Article
- Systemic Inflammation Aggravates Retinal Ganglion Cell Vulnerability to Optic Nerve Trauma in Adult Rats.International journal of molecular sciences · 2026Article
- Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.Investigative ophthalmology & visual science · 2026Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 7 institutions in 4 countries.
Milica A MargetaAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
Zhuoran YinAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Charlotte MadoreAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, F-33000 Bordeaux, France.
Kristen M PittsAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
Sophia M LetcherAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
Jing TangSchepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.
Shuhong JiangSchepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Christian D GauthierAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sebastian R SilveiraAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Caitlin M SchroederAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Eleonora M LadDepartment of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
Alan D ProiaDepartment of Pathology, Duke University Medical Center, Durham, NC, USA; Department of Pathology, Campbell University School of Osteopathic Medicine, Lillington, NC, USA.
Rudolph E TanziGenetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
David M HoltzmanDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer Disease Research Center, Washington University, St. Louis, MO, USA.
Susanne KrasemannInstitute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Dong Feng ChenSchepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Oleg ButovskyAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: obutovsky@rics.bwh.harvard.edu.
Brigham and Women's Hospital · USMassachusetts Eye and Ear Infirmary · USCampbell University · USDuke Medical Center · USHope Center for Neurological Disorders · USMassachusetts General Hospital · USUniversität Hamburg · DE
Funding
VISION RESEARCHP30EY003790 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore · 1985 to 2026
$25.5MMass Eye and Ear-Vision Clinical Scientist Development ProgramK12EY016335 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Reza Dana · 2004 to 2026
$12.3MTargeting TGFb/IFNy-IRF8 Signaling to Modulate Monocytes and their Crosstalk with Microglia and Astrocytes to Treat Multiple SclerosisR01NS088137 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI Oleg Butovsky · 2014 to 2026
$4.9MTargeting the miR-155 and APOE-TREM2 pathways to restore dysfunctional microglia in Alzheimer’s diseaseR01AG054672 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BUTOVSKY, OLEG, IKEZU, TSUNEYA · 2017 to 2021
$4.1MSex-dependent APOE4 regulation of neutrophil-microglia crosstalk in Alzheimer's diseaseR01AG075509 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Oleg Butovsky · 2022 to 2026
$3.6MThe Molecular Basis Underlying Optic Nerve Growth in Development and RegenerationR01EY025259 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI CHEN, DONG FENG · 2016 to 2020
$3.2MMicroglial mechanisms of postoperative CNS inflammation and cognitive declineR01AG051812 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BUTOVSKY, OLEG, CROSBY, GREGORY · 2016 to 2020
$2.7MCognition and the immunology of postoperative outcomesR01GM132668 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI CULLEY, DEBORAH J · 2019 to 2024
$2.7MRole of Microglia in Retinitis PigementosaR01EY027921 · NEI · BRIGHAM AND WOMEN'S HOSPITAL · PI BUTOVSKY, OLEG, HAIDER, NEENA B · 2017 to 2019
$1.5MDevelopment of a Next Generation Visual Performance Assessment System for RodentsR44EY025913 · NEI · AFASCI, INC. · PI CHEN, DONG FENG, LUO, GANG · 2019 to 2020
$1.5MThe Role of APOE Signaling in Microglia in GlaucomaK08EY030160 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI MARGETA, MILICA · 2019 to 2021
$703kIdentification of exosome signature in serum from ALS patientsR21NS104609 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI BERRY, JAMES DALE, BUTOVSKY, OLEG · 2018 to 2019
$543kNEI NIH HHS K08 EY030160NEI NIH HHS K12 EY016335NEI NIH HHS K23 EY026988NEI NIH HHS P30 EY003790NEI NIH HHS R01 EY025259NEI NIH HHS R01 EY027921NEI NIH HHS R41 EY025913NEI NIH HHS R44 EY025913NIA NIH HHS R01 AG051812NIA NIH HHS R01 AG054672NIA NIH HHS R01 AG075509NIA NIH HHS R21 AG076982NIGMS NIH HHS R01 GM132668NINDS NIH HHS R01 NS088137NINDS NIH HHS R21 NS101673NINDS NIH HHS R21 NS104609
Abstract
The apolipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer disease and a decreased risk of glaucoma, but the underlying mechanisms remain poorly understood. Here, we found that in two mouse glaucoma models, microglia transitioned to a neurodegenerative phenotype characterized by upregulation of Apoe and Lgals3 (Galectin-3), which were also upregulated in human glaucomatous retinas. Mice with targeted deletion of Apoe in microglia or carrying the human APOE4 allele were protected from retinal ganglion cell (RGC) loss, despite elevated intraocular pressure (IOP). Similarly to Apoe
Indexed as
Apolipoprotein E4GlaucomaAnimalsApolipoproteins EDisease Models, AnimalGalectin 3HumansMiceMicrogliaApolipoprotein E4Apolipoproteins EGalectin 3Alzheimer diseaseAPOE4Galectin-3glaucomaLgals3microglianeurodegenerationneuroprotectionretina
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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.