Upregulation of Antibody Response to Heat Shock Proteins and Tissue Antigens in an Ocular Ischemia Model
Upregulation of Antibody Response to Heat Shock Proteins and Tissue Antigens in an Ocular Ischemia Model
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DOI：
10.1167/iovs.10-5763
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Grus, Franz H.
中科院分区：
文献类型：
--
作者：
Joachim, Stephanie C.;Wax, Martin B.;Grus, Franz H.
目的。本研究的目的是表征眼缺血再灌注后血清抗体的反应性。检测血清抗体反应的时间过程。将Wistar大鼠眼压升高至130 mm Hg，持续60分钟，造成短暂性眼缺血。2周和4周后观察视神经轴突损伤。在缺血前和缺血后多次采集血液样本，通过定制的蛋白质芯片检测抗体。不同的组织抗原，包括热休克蛋白（HSPs）和晶体蛋白，是根据先前在缺血事件或与缺血相关的眼科疾病研究中鉴定的抗体反应性来选择的。采用多元统计技术比较抗体反应性。眼缺血后2周、4周观察到明显的轴突损伤（P < 0.05）。动物在缺血前对抗原表现出一定的免疫反应，而缺血后许多免疫反应增强。缺血后2周、3周、4周的反应差异有统计学意义（P < 0.05）。抗体对肌动蛋白、胶质纤维酸性蛋白、热休克蛋白27、vimentin或spectrin的反应性持续增加。急性眼压升高引起的缺血导致治疗动物血清中抗体反应性的复杂变化。在4周的随访期间，血清自身抗体，特别是针对热休克和结构蛋白的上调逐渐增加，而泛素等其他抗体则下降。抗热休克蛋白27抗体的上调可能是保护组织免受缺血性损伤的一种尝试。（Invest Ophthalmol Vis Sci. 2011;52:3468-3474） DOI: 10.1167/iovs.10-5763
PURPOSE. The aim of this study was to characterize the serum antibody reactivities occurring after ocular ischemia reperfusion. The time course of serum antibody responses was examined.METHODS. Wistar rats were exposed to transient ocular ischemia by elevating intraocular pressure to 130 mm Hg for 60 minutes. Axonal damage was evaluated on optic-nerve sections 2 and 4 weeks later. Blood samples collected before and several times after ischemia were used for antibody detection via customized protein microarrays. Different tissue antigens, including heat shock proteins (HSPs) and crystallins, were selected based on previous identification of antibody reactivities in studies on ischemic events or ophthalmic diseases associated with ischemia. Antibody reactivity was compared using multivariate statistical techniques.RESULTS. Significant axonal damage was observed 2 and 4 weeks after ocular ischemia (P < 0.05). Animals showed certain immunoreactivities against antigens even before ischemia, whereas many reactivities increased afterward. Significantly different responses were detected 2, 3, and 4 weeks after ischemia (P < 0.05). Antibody reactivity against actin, glial fibrillary acidic protein, HSP 27, vimentin, or spectrin continually increased.CONCLUSIONS. Ischemia induced by acute intraocular pressure elevation led to complex changes in antibody reactivities in sera of treated animals. Upregulation of serum autoantibodies, especially against heat shock and structural proteins, progressively increased throughout the 4-week follow-up period, whereas others such as ubiquitin decreased. The upregulation of anti-HSP 27 antibodies might be an attempt to protect the tissue from ischemic damage. (Invest Ophthalmol Vis Sci. 2011;52:3468-3474) DOI: 10.1167/iovs.10-5763