Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP
Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP
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DOI：
10.1111/j.1460-9568.2007.05528.x
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发表时间：
2007-05-01
影响因子：
3.4
通讯作者：
Galli-Resta, Lucia
中科院分区：
文献类型：
--
作者：
Resta, Valentina;Novelli, Elena;Galli-Resta, Lucia
高眼压可能导致视网膜神经节细胞损伤，进而导致视力障碍。慢性眼压升高是青光眼的主要危险因素，青光眼是一种主要的致盲疾病，由于创伤、急性青光眼或屈光手术导致的急性眼压升高也可能导致永久性视力障碍。压力是如何影响视网膜神经元的还没有确定下来。视神经头的机械性损伤、血液供应减少、炎症和细胞毒性因素都起到了作用。由于在压力增加后不久对视网膜神经元的分析将提供有用的线索，我们在短暂的静水压力增加之前和之后对分离的大鼠视网膜中的单个神经节细胞进行了成像。我们发现，在创伤、急性青光眼或屈光手术中，压力缓慢上升至峰值(50-90毫米汞柱)不会损伤神经节细胞，而快速脉冲至50毫米汞柱则在1小时内损伤30%的神经节细胞。损伤的严重程度和受影响的细胞数量随着更强或重复的侮辱而增加。降解胞外ATP或阻断ATIP的P2X受体可预防急性压力所致的神经节细胞损伤。在体内也观察到了类似的效果。短暂的眼压瞬变在1h内增加了眼液中的细胞外ATP水平和受损的神经节细胞，减少了眼内的细胞外ATP，防止了神经节细胞的损伤，加速了神经节细胞对光的反应。这些数据表明，快速压力瞬变导致急性神经节细胞损伤，并揭示了细胞外ATP升高在这种损伤中的原因作用。
Elevated intraocular pressure may lead to retinal ganglion cell injury and consequent visual deficits. Chronic intraocular pressure increase is a major risk factor for glaucoma, a leading blinding disease, and permanent visual deficits can also occur following acute pressure increments due to trauma, acute glaucoma or refractive surgery. How pressure affects retinal neurons is not firmly established. Mechanical damage at the optic nerve head, reduced blood supply, inflammation and cytotoxic factors have all been called into play. Reasoning that the analysis of retinal neurons soon after pressure elevation would provide useful cues, we imaged individual ganglion cells in isolated rat retinas before and after short hydrostatic pressure increments. We found that slowly rising pressure to peaks observed in trauma, acute glaucoma or refractive surgery (50-90 mmHg) did not damage ganglion cells, whereas a rapid 1 min pulse to 50 mmHg injured 30% of these cells within 1 h. The severity of damage and the number of affected cells increased with stronger or repeated insults. Degrading extracellular ATP or blocking the P2X receptors for ATIP prevented acute pressure-induced damage in ganglion cells. Similar effects were observed in vivo. A short intraocular pressure transient increased extracellular ATP levels in the eye fluids and damaged ganglion cells within 1 h. Reducing extracellular ATP in the eye prevented damage to ganglion cells and accelerated recovery of their response to light. These data show that rapid pressure transients induce acute ganglion cell injury and unveil the causal role of extracellular ATP elevation in such injury.