title: Retinal Pre-Conditioning by CD59a Knockout Protects against Light-Induced Photoreceptor Degeneration.
abstract: Complement dysregulation plays a key role in the pathogenesis of age-related macular degeneration (AMD), but the specific mechanisms are incompletely understood. Complement also potentiates retinal degeneration in the murine light damage model. To test the retinal function of CD59a, a complement inhibitor, CD59a knockout (KO) mice were used for light damage (LD) experiments. Retinal degeneration and function were compared in WT versus KO mice following light damage. Gene expression changes, endoplasmic reticulum (ER) stress, and glial cell activation were also compared. At baseline, the ERG responses and rhodopsin levels were lower in CD59aKO compared to wild-type (WT) mice. Following LD, the ERG responses were better preserved in CD59aKO compared to WT mice. Correspondingly, the number of photoreceptors was higher in CD59aKO retinas than WT controls after LD. Under normal light conditions, CD59aKO mice had higher levels than WT for GFAP immunostaining in Müller cells, mRNA and protein levels of two ER-stress markers, and neurotrophic factors. The reduction in photon capture, together with the neurotrophic factor upregulation, may explain the structural and functional protection against LD in the CD59aKO.
authors.affiliation: The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.
authors.forename: Delu
authors.identifier: http://orcid.org/0000-0002-9030-7211
authors.initials: D
authors.lastname: Song
authors.affiliation: Department of Ophthalmology, Medical University of South Carolina, Charleston, SC.
authors.forename: Brooks
authors.initials: B
authors.lastname: Wilson
authors.affiliation: The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.|Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.
authors.forename: Rupak
authors.initials: R
authors.lastname: Bhuyan
authors.affiliation: Department of Ophthalmology, Medical University of South Carolina, Charleston, SC.
authors.forename: Mausumi
authors.initials: M
authors.lastname: Bandyopadhyay
authors.affiliation: The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.
authors.forename: Arkady
authors.initials: A
authors.lastname: Lyubarsky
authors.affiliation: Center for Cancer, Genetic Diseases, and Gene Regulation, Department of Biological Sciences, Fordham University, Bronx, NY.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.
authors.forename: Levi
authors.initials: L
authors.lastname: Kanu
authors.affiliation: Department of Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miwa
authors.affiliation: Department of Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Song
authors.affiliation: Center for Cancer, Genetic Diseases, and Gene Regulation, Department of Biological Sciences, Fordham University, Bronx, NY.
authors.forename: Silvia C
authors.initials: SC
authors.lastname: Finnemann
authors.affiliation: Department of Ophthalmology, Medical University of South Carolina, Charleston, SC.|Research Service, Ralph H. Johnson VA Medical Center, Charleston, SC.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Rohrer
authors.affiliation: The F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Dunaief
mesh_terms: D000818:Animals; D018957:CD59 Antigens / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000528:radiation effects; D063928:Ependymoglial Cells / Q000378:metabolism; D015353:Eye Enucleation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008027:Light; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D010587:Phagocytosis / Q000528:radiation effects; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000528:radiation effects*; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000000981:diagnostic imaging / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology* / Q000662:veterinary; D012172:Retinaldehyde / Q000032:analysis; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: D018957:CD59 Antigens; C539311:CD59a protein, mouse; D016207:Cytokines; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D012243:Rhodopsin; D012172:Retinaldehyde