Structural basis of glaucoma: The fortified astrocytes of the optic nerve head are the target of raised intraocular pressure
Structural basis of glaucoma: The fortified astrocytes of the optic nerve head are the target of raised intraocular pressure
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作者：
Dai, Chao;Khaw, Peng T.;Li, Ying
高眼压(IOP)会损害穿过视神经头(ONH)的视网膜神经节细胞轴突。人类筛板的巨大结缔组织结构通常被认为是造成损伤的压力传感器。然而，没有筛板的大鼠对眼压升高也有同样的青光眼反应。在这里，我们展示了大鼠ONH的星形胶质细胞由非常密集的细胞骨架细丝加强，这将使它们成为扭曲机械力的理想传感器。ONH星形胶质细胞呈扇形放射状排列，腹侧由厚厚的基底突牢牢地附着在ONH鞘上，但在背侧分成逐渐细长的突起，仅在鞘上有微妙的附着。在前房注射磁性微球升高眼压的1周时，ONH星形胶质细胞的细小背突从周围的鞘中剥离。没有轴突变形或受压的迹象。随后，尽管眼压恢复到正常水平，但ONH的损害通过星形细胞小体向腹侧发展，导致强化的星形胶质细胞和大部分轴突在大约4周内完全丧失。我们认为，在青光眼中，星形胶质细胞的背部附着是最初损伤的部位，轴突的损伤不是机械性的，而是星形胶质细胞局部代谢支持丧失的结果(Tacopoulos和Magistretti(1996年)J Neurosci 16：877885)。(C)2011年威利期刊公司。
Increased intraocular pressure (IOP) damages the retinal ganglion cell axons as they pass through the optic nerve head (ONH). The massive connective tissue structure of the human lamina cribrosa is generally assumed to be the pressure transducer responsible for the damage. The rat, however, with no lamina cribrosa, suffers the same glaucomatous response to raised IOP. Here, we show that the astrocytes of the rat ONH are fortified by extraordinarily dense cytoskeletal filaments that would make them ideal transducers of distorting mechanical forces. The ONH astrocytes are arranged as a fan-like radial array, firmly attached ventrally to the sheath of the ONH by thick basal processes, but dividing dorsally into progressively more slender processes with only delicate attachments to the sheath. At 1 week after raising the IOP by an injection of magnetic microspheres into the anterior eye chamber, the fine dorsal processes of the ONH astrocytes are torn away from the surrounding sheath. There is no indication of distortion or compression of the axons. Subsequently, despite return of the IOP toward normal levels, the damage to the ONH progresses ventrally through the astrocytic cell bodies, resulting in complete loss of the fortified astrocytes and of the majority of the axons by around 4 weeks. We propose that the dorsal attachments of the astrocytes are the site of initial damage in glaucoma, and that the damage to the axons is not mechanical, but is a consequence oflocalized loss of metabolic support from the astrocytes (Tsacopoulos and Magistretti (1996) J Neurosci 16:877885). (c) 2011 Wiley Periodicals, Inc.