Increased Lipocalin-2 in the retinal pigment epithelium of Cryba1 cKO mice is associated with a chronic inflammatory response.

Mallika Valapala, Malia Edwards, Stacey Hose, Rhonda Grebe, Imran A Bhutto, Marisol Cano, Thorsten Berger, Tak W Mak, Eric Wawrousek, James T Handa, Gerard A Lutty, J Samuel Zigler, Debasish Sinha

Aging cell 2014 Dec

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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. © 2014 The Authors. Aging Cell publisshed by the Anatomical Society and John Wiley & Sons Ltd.

Citation

Mallika Valapala, Malia Edwards, Stacey Hose, Rhonda Grebe, Imran A Bhutto, Marisol Cano, Thorsten Berger, Tak W Mak, Eric Wawrousek, James T Handa, Gerard A Lutty, J Samuel Zigler, Debasish Sinha. Increased Lipocalin-2 in the retinal pigment epithelium of Cryba1 cKO mice is associated with a chronic inflammatory response. Aging cell. 2014 Dec;13(6):1091-4