title: A Non-Canonical Role for β-Secretase in the Retina.
abstract: It has long been established that β-Secretase (BACE) plays a critical role in the formation of amyloid plaques in Alzheimer's Disease patients, but it is only recently that the importance of β-secretases in retinal pathophysiology has been recognized. BACE expression is elevated in response to stress, and downregulation results in lysosomal abnormalities and mitochondrial changes. Inhibition of BACE can lead to reduced retinal function, retinal thinning, lipofuscin accumulation and vascular dysfunction in mice. Furthermore, BACE inhibition accelerates choroidal neovascularization (CNV) in mice. We propose that BACE plays an important role in retinal homeostasis and that BACE upregulation in response to stress is a protective measure.
authors.affiliation: Department of Ophthalmology, Indiana University, 980 Walnut Street, R3-426A, 46202, Indianapolis, IN, USA. qiank@iupui.edu.
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Qian
authors.affiliation: Department of Ophthalmology, Indiana University, 980 Walnut Street, R3-426A, 46202, Indianapolis, IN, USA. skmitter@iupui.edu.
authors.forename: Sayak K
authors.initials: SK
authors.lastname: Mitter
authors.affiliation: Department of Ophthalmology, Indiana University, 980 Walnut Street, R3-426A, 46202, Indianapolis, IN, USA. slpay@iupui.edu.|Department of Medical and Molecular Genetics, Indiana University School of Medicine, 46202, Indianapolis, IN, USA. slpay@iupui.edu.
authors.forename: S Louise
authors.initials: SL
authors.lastname: Pay
authors.affiliation: Department of Ophthalmology, Indiana University, 980 Walnut Street, R3-426A, 46202, Indianapolis, IN, USA. qixi@iupui.edu.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qi
authors.affiliation: Departments of Ophthalmology and of Cell Biology, Duke University Medical Center, Durham, 27710, NC, USA. bowes007@duke.edu.
authors.forename: Catherine Bowes
authors.initials: CB
authors.lastname: Rickman
authors.affiliation: Department of Ophthalmology, Indiana University, 980 Walnut Street, R3-426A, 46202, Indianapolis, IN, USA. mabgrant@iupui.edu.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
authors.affiliation: Department of Ophthalmology, Indiana University, 980 Walnut Street, R3-426A, 46202, Indianapolis, IN, USA. mboulton@iupui.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Boulton
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000503:physiopathology; D004195:Disease Models, Animal; D006706:Homeostasis; D006801:Humans; D008268:Macular Degeneration / Q000201:enzymology / Q000503:physiopathology; D051379:Mice; D012160:Retina / Q000201:enzymology* / Q000503:physiopathology
chemical_list: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human
keywords: Age-related macular degeneration; Angiogenesis; Choroidal neovascularisation; Lysosomes; Mitochondria; Retinal degeneration; Retinal pigment epithelium; β-secretase