ArticleCell reports2015
ROCK-isoform-specific polarization of macrophages associated with age-related macular degeneration.
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Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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104citing papers in PubMed
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104 citing papers in PubMed, 188 citations in OpenAlex.
- Inhibition of ROCK2 via KD025/Belumosudil Alleviates Hypertensive End-Organ Damage.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Donor macrophage depletion permits posttransplant tolerance induction in a murine islet transplant model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Exploring Endotoxemia in Age-Related Macular Degeneration, Glaucoma, and Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Review
- Implications of Rho GTPase signaling in cancer immunotherapy.Biochemical Society transactions · 2026Review
- Adipocytes influence choroidal neovascularization via PRDM16.EMBO molecular medicine · 2026Article
- TNFAIP3 in M2 Macrophage Attenuates Subretinal Fibrosis in Laser-Induced Murine Model.Investigative ophthalmology & visual science · 2026Article
- RPE With ROCK-Mediated Epithelial-Mesenchymal Transition as a Key Contributor of Subretinal Fibrosis in AMD.Investigative ophthalmology & visual science · 2026Article
- Histone demethylase KDM7A negatively regulates fibrotic macrophage polarization and lung fibrosis progression.Communications biology · 2026Article
- CU104, a novel barrier function enhancer, improves colitis via modulation of barrier function and immune cell recruitment.Frontiers in immunology · 2026Article
- Rho-kinase inhibition reduces subretinal fibrosis.Cell death discovery · 2025Article
- En-face quantitative evaluation using ultra-high-resolution OCT of hyperreflective foci in neovascular age-related macular degeneration.Japanese journal of ophthalmology · 2025Observational
- Triamcinolone Acetonide Protects Against Light-Induced Retinal Degeneration by Activating Anti-Inflammatory STAT6/Arg1 Signaling in Microglia.Inflammation · 2025Article
- Adrb2 Expression in Ocular-Infiltrating Macrophages Is Necessary for Interleukin-6 Expression and Choroidal Neovascularization.Investigative ophthalmology & visual science · 2025Article
- Dynamic hierarchical ligand anisotropy for competing macrophage regulationBioactive materials · 2025Article
- The Landscape of Vascular Endothelial Growth Factor Inhibition in Retinal Diseases.Investigative ophthalmology & visual science · 2025Review
- The pathophysiological mechanisms of immunosenescence in coronary artery disease.Frontiers in cell and developmental biology · 2025Review
- Macrophages and Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2025Review
- Review
- A New Modulator of Neuroinflammation in Diabetic Retinopathy: USP25.Inflammation · 2024Article
- Sema4D Knockout Attenuates Choroidal Neovascularization by Inhibiting M2 Macrophage Polarization Via Regulation of the RhoA/ROCK Pathway.Investigative ophthalmology & visual science · 2024Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 11 institutions in 6 countries.
Souska ZandiCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Swiss Eye Institute, Rotkreuz and Berner Augenklinik am Lindenhofspital, 3012 Bern, Switzerland.
Shintaro NakaoCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Kwang-Hoon ChunGachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Incheon 406-799, Republic of Korea.
Paolo FiorinaNephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Transplant Medicine, San Raffaele Hospital, 20132 Milan, Italy.
Dawei SunCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, the First and Second Affiliated Hospitals of the Harbin Medical University, Harbin 150086, China.
Ryoichi AritaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Ming ZhaoCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; State Key Laboratory of Oncology, Minimally Invasive Interventional Division, Medical Imaging Center, Sun Yat-Sen University, Guangzhou 510060, China.
Enoch KimSurface Logix, Inc., 50 Soldiers Field Place, Brighton, MA 02135, USA.
Olivier SchuellerSurface Logix, Inc., 50 Soldiers Field Place, Brighton, MA 02135, USA.
Stewart CampbellSurface Logix, Inc., 50 Soldiers Field Place, Brighton, MA 02135, USA.
Mahdi TaherCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.
Mark Ivan MelhornCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.
Alexander ScheringCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA.
Francesca GattiNephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Transplant Medicine, San Raffaele Hospital, 20132 Milan, Italy.
Sara TezzaNephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Transplant Medicine, San Raffaele Hospital, 20132 Milan, Italy.
Fang XieCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA; Department of Ophthalmology, the First and Second Affiliated Hospitals of the Harbin Medical University, Harbin 150086, China.
Andrea VerganiNephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Transplant Medicine, San Raffaele Hospital, 20132 Milan, Italy.
Shigeo YoshidaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Keijiro IshikawaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Muneo YamaguchiDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Fumiyuki SasakiDepartment of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Ruth Schmidt-UllrichDepartment of Signal Transduction in Tumor Cells, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Straße 10, 13092 Berlin, Germany.
Yasuaki HataDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Hiroshi EnaidaDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Mitsuko YuzawaDepartment of Ophthalmology, School of Medical Sciences, Nihon University, Tokyo 173-8610, Japan.
Takehiko YokomizoDepartment of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Young-Bum KimDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Paul SweetnamSurface Logix, Inc., 50 Soldiers Field Place, Brighton, MA 02135, USA.
Tatsuro IshibashiDepartment of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Ali Hafezi-MoghadamCenter for Excellence in Functional and Molecular Imaging, Brigham & Women's Hospital, Boston, MA 02115, USA; Department of Radiology, Harvard Medical School, Boston, MA 02115, USA; Angiogenesis Laboratory, Massachusetts Eye & Ear Infirmary, Boston, MA 02114, USA; Department of Ophthalmology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ahm@bwh.harvard.edu.
Kyushu University · JPBoston Children's Hospital · USBrigham and Women's Hospital · USMassachusetts Eye and Ear Infirmary · USHarvard University · USJuntendo University · JPBeth Israel Deaconess Medical Center · USGachon University · KRMax Delbrück Center · DENihon University · JPSun Yat-sen University · CN
Funding
ROCK1 Signaling in Glucose MetabolismR01DK083567 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KIM, YOUNG-BUM · 2010 to 2018
$3.4MNon-Invasive Molecular Imaging in Early Diagnosis of Diabetic ComplicationsDP3DK108238 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI HAFEZI-MOGHADAM, ALI · 2015 to 2015
$1.7MNIDDK NIH HHS DP3 DK108238NIDDK NIH HHS R01 DK083567NIDDK NIH HHS R01DK083567
Abstract
Age is a major risk factor in age-related macular degeneration (AMD), but the underlying cause is unknown. We find increased Rho-associated kinase (ROCK) signaling and M2 characteristics in eyes of aged mice, revealing immune changes in aging. ROCK isoforms determine macrophage polarization into M1 and M2 subtypes. M2-like macrophages accumulated in AMD, but not in normal eyes, suggesting that these macrophages may be linked to macular degeneration. M2 macrophages injected into the mouse eye exacerbated choroidal neovascular lesions, while M1 macrophages ameliorated them, supporting a causal role for macrophage subtypes in AMD. Selective ROCK2 inhibition with a small molecule decreased M2-like macrophages and choroidal neovascularization. ROCK2 inhibition upregulated M1 markers without affecting macrophage recruitment, underlining the plasticity of these macrophages. These results reveal age-induced innate immune imbalance as underlying AMD pathogenesis. Targeting macrophage plasticity opens up new possibilities for more effective AMD treatment.
Indexed as
AgingAnimalsBone Marrow CellsCell DifferentiationCell PolarityCells, CulturedChoroidChoroidal NeovascularizationCytokinesHumansMacrophagesMacular DegenerationMaleMiceMice, Inbred C57BLNF-kappa BCytokinesNF-kappa Brho-Associated KinasesRock1 protein, mouseRock2 protein, mouse
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