title: Increased Lipocalin-2 in the retinal pigment epithelium of Cryba1 cKO mice is associated with a chronic inflammatory response.
abstract: Although chronic inflammation is believed to contribute to the pathology of age-related macular degeneration (AMD), knowledge regarding the events that elicit the change from para-inflammation to chronic inflammation in the pathogenesis of AMD is lacking. We propose here that lipocalin-2 (LCN2), a mammalian innate immunity protein that is trafficked to the lysosomes, may contribute to this process. It accumulates significantly with age in retinal pigment epithelial (RPE) cells of Cryba1 conditional knockout (cKO) mice, but not in control mice. We have recently shown that these mice, which lack βA3/A1-crystallin specifically in RPE, have defective lysosomal clearance. The age-related increase in LCN2 in the cKO mice is accompanied by increases in chemokine (C-C motif) ligand 2 (CCL2), reactive gliosis, and immune cell infiltration. LCN2 may contribute to induction of a chronic inflammatory response in this mouse model with AMD-like pathology.
authors.affiliation: Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Mallika
authors.initials: M
authors.lastname: Valapala
authors.forename: Malia
authors.initials: M
authors.lastname: Edwards
authors.forename: Stacey
authors.initials: S
authors.lastname: Hose
authors.forename: Rhonda
authors.initials: R
authors.lastname: Grebe
authors.forename: Imran A
authors.initials: IA
authors.lastname: Bhutto
authors.forename: Marisol
authors.initials: M
authors.lastname: Cano
authors.forename: Thorsten
authors.initials: T
authors.lastname: Berger
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Eric
authors.initials: E
authors.lastname: Wawrousek
authors.forename: James T
authors.initials: JT
authors.lastname: Handa
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Lutty
authors.forename: J
authors.initials: J
authors.lastname: Samuel Zigler
authors.forename: Debasish
authors.initials: D
authors.lastname: Sinha
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D002908:Chronic Disease; D003459:Crystallins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008268:Macular Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D015513:Oncogene Proteins / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D038205:beta-Crystallin A Chain
chemical_list: D000209:Acute-Phase Proteins; C051374:Cryba1 protein, mouse; D003459:Crystallins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D038205:beta-Crystallin A Chain; C071332:Lcn2 protein, mouse
keywords: Cryba1 cKO mice, inflammation; age-related macular degeneration; lipocalin-2; lysosomes; retinal pigment epithelium