Knockout of Ccr2 alleviates photoreceptor cell death in rodent retina exposed to chronic blue light.
Age-related macular degeneration (AMD), the leading cause of visual loss after the age of 60 years, is a degenerative retinal disease involving a variety of environmental and hereditary factors. Although it has been implicated that immune system is involved in the disease progression, the exact role that microglia has is still unclear. Here we demonstrated that knockout of Ccr2 gene could alleviate photoreceptor cell death in mice retinas exposed to chronic blue light. In Ccr2-/-mice, a damaged microglia recruitment was shown in retina and this could protect the visual function in electroretinogram and alleviate the photoreceptor apoptosis, which thus helped attenuate the blue light-induced retinopathy. We further found an increased co-location of NLRP3, Iba-1, and IL-1β in fluorescence and a concomitant increased protein expression of NLRP3, caspase-1, and IL-1β in western blotting in chronic blue light-induced retinopathy. Moreover, the activation of microglia and their cellular NLRP3 inflammasomes occurred as an earlier step before the structural and functional damage of the mice retinas, which collectively supported that microglial NLRP3 inflammasome might be the key to the chronic blue light-induced retinopathy.
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zizhong
Z
Hu
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yi
Y
Zhang
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Junling
J
Wang
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Pingan
P
Mao
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Xuehua
X
Lv
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Songtao
S
Yuan
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zhengru
Z
Huang
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yuzhi
Y
Ding
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Ping
P
Xie
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Qinghuai
Q
Liu
D000818:Animals; D015153:Blotting, Western; D020170:Caspase 1 / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects; D004596:Electroretinography; D005455:Fluorescent Antibody Technique; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008027:Light; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology*; D054390:Receptors, CCR2 / Q000172:deficiency* / Q000378:metabolism; D012160:Retina / Q000473:pathology* / Q000503:physiopathology / Q000528:radiation effects*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology; D014785:Vision, Ocular / Q000528:radiation effects
C515335:Ccr2 protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D054390:Receptors, CCR2; D020170:Caspase 1