Leukocyte chemotactic receptor Fpr1 protects against aging‐related posterior subcapsular cataract formation. Issue 2 (4th February 2021)

• Record Type: Journal Article
• Authors: Gao, Ji‐Liang; Weaver, Joseph D.; Tuo, Jingsheng; Wang, Long Q.; Siwicki, Marie; Despres, Daryl; Lizak, Martin; Schneider, Erich H.; Kovacs, William; Maminishkis, Arvydas; Chen, Keqiang; Yoshimura, Teizo; Ming Wang, Ji; Chao Chan, Chi; Murphy, Philip M.
• Is Part Of: FASEB journal. Volume 35:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-02-04
• Subjects: cataract -- chemoattractant receptor -- eye -- formyl peptide -- G protein -- knockout mouse; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202002135R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: 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.