Title | CD4 positive T helper cells contribute to retinal ganglion cell death in mouse model of ischemia reperfusion injury |
Authors | Huang, Ping Huo, Yanjiao Lou, Lucy X. Li, Hong Barnstable, Colin J. Zhang, Chun Zhang, Samuel S. |
Affiliation | Peking Univ, Peking Univ Hosp 3, Ctr Eye, Dept Ophthalmol, Beijing 100191, Peoples R China. Penn State Univ, Dept Neural & Behav Sci, Hershey, PA 17033 USA. Penn State Univ, Penn State Hershey Eye Ctr, Hershey, PA 17033 USA. Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore. |
Keywords | retinal ganglion cell immune T helper cell severe combined immunodeficient mice neuroprotection ischemia STAT6 NECROSIS-FACTOR-ALPHA HEAT-SHOCK PROTEINS OPEN-ANGLE GLAUCOMA OPTIC-NERVE HEAD BRAIN-INJURY CEREBRAL-ISCHEMIA NEURONAL SURVIVAL STAT3 ACTIVATION IMMUNE-SYSTEM REGENERATION |
Issue Date | 2013 |
Publisher | experimental eye research |
Citation | EXPERIMENTAL EYE RESEARCH.2013,115,131-139. |
Abstract | Neuron degeneration is a common pathological process associated with many disease conditions in the central nervous system including retina. Although immune responses have been proposed as one potential element in triggering neural damage, the mechanism of action of specific immune components underlying the pathogenesis is unclear. In this study we focus on adaptive immune activities to evaluate CD4 positive helper cells in the retinal ganglion cell (RGC) degeneration in response to transient retinal ischemic/reperfusion (I/R) injury. Transient retinal ischemia was induced in four mouse strains with different immune backgrounds, including wild type mice from C57BL/6 and BABL/c strains, severe combined immunodeficient (SCID) mice lacking T and B lymphocytes, SCID mice with transferred wild type CD4+ T cells, and the STAT6 deficient mice without T helper 2 (TH2) cells. In SCID mice RGCs showed a strong resistance to cell death in response to I/R injury (89% +/- 3% of the survival cells in contralateral eye) compared with C57BL/6 (p = 0.018) and BALB/C (p = 0.038) wild types. By transferring the mature CD4+ T cells from matched wild type into SCID mice, the resistance of RGCs to injury was significantly compromised (p < 0.05). Furthermore a significant resistance of RGCs to cell death (p < 0.05) accompanied with an overexpression of STAT1 and STAT3 was confirmed in STAT6 deficient mice in response to I/R injury compared with the wild type controls, indicating that TH2 cells maturation might be involved in RGC damage. Adaptive immunity carried by CD4 T cells plays an essential role in RGC degeneration. (C) 2013 Elsevier Ltd. All rights reserved. |
URI | http://hdl.handle.net/20.500.11897/190504 |
ISSN | 0014-4835 |
DOI | 10.1016/j.exer.2013.06.015 |
Indexed | SCI(E) PubMed |
Appears in Collections: | 第三医院 |