TY - JOUR
T1 - Retinal Pre-conditioning by CD59a knockout protects against light-induced photoreceptor degeneration
AU - Song, Delu
AU - Wilson, Brooks
AU - Zhao, Liangliang
AU - Bhuyan, Rupak
AU - Bandyopadhyay, Mausumi
AU - Lyubarsky, Arkady
AU - Yu, Chen
AU - Li, Yafeng
AU - Kanu, Levi
AU - Miwa, Takashi
AU - Song, Wen Chao
AU - Finnemann, Silvia C.
AU - Rohrer, Bärbel
AU - Dunaief, Joshua L.
N1 - Publisher Copyright:
© 2016 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/11
Y1 - 2016/11
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84999048255
U2 - 10.1371/journal.pone.0166348
DO - 10.1371/journal.pone.0166348
M3 - Article
C2 - 27893831
AN - SCOPUS:84999048255
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e0166348
ER -