Leukocyte chemotactic receptor Fpr1 protects against aging-related posterior subcapsular cataract formation.

Autor: Gao JL; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Weaver JD; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Tuo J; Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA., Wang LQ; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Siwicki M; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Despres D; Mouse Imaging Facility, National Institutes of Health, Bethesda, MD, USA., Lizak M; Mouse Imaging Facility, National Institutes of Health, Bethesda, MD, USA., Schneider EH; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Kovacs W; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Maminishkis A; Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD, USA., Chen K; Laboratory of Cancer and Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA., Yoshimura T; Department of Pathology and Experimental Medicine, Okayama University, Okayama, Japan., Ming Wang J; Laboratory of Cancer and Immunometabolism, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA., Chao Chan C; Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA., Murphy PM; Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Feb; Vol. 35 (2), pp. e21315.
DOI: 10.1096/fj.202002135R
Abstrakt: Cataracts are a common consequence of aging; however, pathogenesis remains poorly understood. Here, we observed that after 3 months of age mice lacking the G protein-coupled leukocyte chemotactic receptor Fpr1 (N-formyl peptide receptor 1) began to develop bilateral posterior subcapsular cataracts that progressed to lens rupture and severe degeneration, without evidence of either systemic or local ocular infection or inflammation. Consistent with this, Fpr1 was detected in both mouse and human lens in primary lens epithelial cells (LECs), the only cell type present in the lens; however, expression was confined to subcapsular LECs located along the anterior hemispheric surface. To maximize translucency, LECs at the equator proliferate and migrate posteriorly, then differentiate into lens fiber cells by nonclassical apoptotic signaling, which results in loss of nuclei and other organelles, including mitochondria which are a rich source of endogenous N-formyl peptides. In this regard, denucleation and posterior migration of LECs were abnormal in lenses from Fpr1 -/- mice, and direct stimulation of LECs with the prototypic N-formyl peptide agonist fMLF promoted apoptosis. Thus, Fpr1 is repurposed beyond its immunoregulatory role in leukocytes to protect against cataract formation and lens degeneration during aging.
(Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)
Databáze: MEDLINE
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