Programmed cell death-1 is expressed in large retinal ganglion cells and is upregulated after optic nerve crush.
Programmed cell death-1 (PD-1) is a key negative receptor inducibly expressed on T cells, B cells and dendritic cells. It was discovered on T cells undergoing classical programmed cell death. Studies showed that PD-1 ligation promotes retinal ganglion cell (RGC) death during retinal development. The purpose of this present study is to characterize PD-1 regulation in the retina after optic nerve crush (ONC). C57BL/6 mice were subjected to ONC and RGC loss was monitored by immunolabelling with RNA-binding protein with multiple splicing (Rbpms). Time course of PD-1 mRNA expression was determined by real-time PCR. PD-1 expression was detected with anti-PD-1 antibody on whole mount retinas. PD-1 staining intensity was quantitated. Colocalization of PD-1 and cleaved-caspase-3 after ONC was analyzed. Real-time PCR results demonstrated that PD-1 gene expression was significantly upregulated at day 1, 3, 7, 10 and 14 after ONC. Immunofluorescent staining revealed a dramatic increase of PD-1 expression following ONC. In both control and injured retinas, PD-1 tended to be up-expressed in a subtype of RGCs, whose somata size were significantly larger than others. Compared to control, PD-1 intensity in large RGCs was increased by 82% in the injured retina. None of the large RGCs expressed cleaved-caspase-3 at day 5 after ONC. Our work presents the first evidence of PD-1 induction in RGCs after ONC. This observation supports further investigation into the role of PD-1 expression during RGC death or survival following injury.
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States; Fudan Affiliated Eye and ENT Hospital, Fenyang Road 83#, Shanghai 200031, China.
Wei
W
Wang
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States.
Ann
A
Chan
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States.
Yu
Y
Qin
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States.
Jacky M K
JMK
Kwong
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States.
Joseph
J
Caprioli
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States.
Ralph
R
Levinson
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States; Fudan Affiliated Eye and ENT Hospital, Fenyang Road 83#, Shanghai 200031, China. Electronic address: linglingchen98@hotmail.com.
Ling
L
Chen
Jules Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, United States. Electronic address: lgordon@mednet.ucla.edu.
Lynn K
LK
Gordon
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009409:Nerve Crush; D020221:Optic Nerve Injuries / Q000235:genetics* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D015398:Signal Transduction
C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger; C505409:Casp3 protein, mouse; D053148:Caspase 3
Apoptosis; Large retinal ganglion cells; Neuroprotection; Optic nerve crush; Programmed cell death-1