High pressure-induced retinal ischaemia reperfusion causes upregulation of gap junction protein connexin43 prior to retinal ganglion cell loss

被引:52
作者
Kerr, Nathan M. [1 ]
Johnson, Cameron S. [1 ]
Zhang, Jie [1 ]
Eady, Elizabeth K. [1 ]
Green, Colin R. [1 ]
Danesh-Meyer, Helen V. [1 ]
机构
[1] Univ Auckland, Dept Ophthalmol, Fac Med & Hlth Sci, Auckland Mail Ctr, Auckland 1142, New Zealand
关键词
Retina ischaemia; Gap junctions; Astrocytes; Retinal ganglion cells; Connexin43; SPINAL-CORD-INJURY; OPTIC-NERVE CRUSH; INTERCELLULAR COMMUNICATION; EXPRESSION PATTERNS; EFFECTIVE REDUCTION; RODENT MODEL; ALBINO-RATS; BRAIN; DEATH; IMMUNOREACTIVITY;
D O I
10.1016/j.expneurol.2011.12.027
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We aimed to characterise the spatial and temporal expression of connexin43 (Cx43) following retinal ischaemia-reperfusion injury and to evaluate its relationship to retinal glial response and subsequent retinal ganglion cell loss. Unilateral retinal ischaemia-reperfusion injury was induced by elevating intraocular pressure to 120 mm Hg for 60 min and then normalized in Wistar rats. Retinas (n = 110) were evaluated at 4, 8, and 24 h, and 7, 14, and 21 days in 4 groups: ischaemic, contralateral, sham operated, and uninjured eyes. Immunohistochemistry was used to analyse the spatial and cell-specific expression of Cx43 protein, glial fibrillary acidic protein (astrocytes). glutamine synthetase (Muller cells), Isolectin B4 (vascular endothelium), DAPI (nuclear marker), and BRN3a (retinal ganglion cells). Retinal whole mounts were used to count retinal ganglion cells. Our results show that Cx43 immunoreactivity of the ischaemic eye is significantly increased in the ganglion cell layer and nerve fibre layer, colocalizing with activated retinal astrocytes and Muller cells at 8 h. In the inner retinal layers Cx43 was also upregulated and colocalized with retinal vascular endothelium at 4, 8 and 24 h post ischaemia. Notably, in the contralateral eye, Cx43 immunoreactivity was also significantly increased in the ganglion cell layer and nerve fibre layer at 8 and 24 h, and at 4 h in the inner layers. Sham operated controls did not show any change in Cx43 immunoreactivity. Subsequently a significant retinal ganglion cell loss was observed in the ischaemic eye at day 21 with a trend towards retinal ganglion cell loss in the contralateral eye. In conclusion, upregulation of Cx43 occurs in both the ischaemic and contralateral retinas although far more significantly in injured retinas. Cx43 colocalizes primarily with activated retinal astrocytes and Muller cells as well as vascular endothelium, suggesting that gap junction communication and/or hemichannel activity may be a mediator of inflammation, vascular permeability, and subsequently neuronal death. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:144 / 152
页数:9
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