Zhang Y, Stone J
Department of Anatomy and Histology, New South Wales Retinal Dystrophy Research Centre, Australia.
Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1653-66.
To assess the role of astrocytes in controlling the growth of developing retinal vessels.
Growth of retinal vessels in the neonatal rat retina was examined in three conditions: normal development, cyclic hyperoxia, and normoxia (1 day 70% to 75% oxygen, 1 day room air for up to seven cycles from birth, and room air for up to 16 days), and direct hypoxia (10% oxygen from postnatal day 3 [P3]). Retinas were examined as wholemounts labeled for astrocytes, microglia, and blood vessels and in some experiments for the fragmentation of DNA characteristic of apoptosis.
In normoxia, superficial retinal vessels formed to the processes of astrocytes. In cyclic hyperoxia, the depletion of superficial retinal vessels and subsequent neovascularization described by others were confirmed. The neovascularization was preceded by the depletion by apoptotic death of the astrocyte population, first between vessels but eventually breaching the glia limitans along vessels. The earliest forms of neovascularization resembled microaneurysms, each protruding through a defect in the glia limitans of a capillary. Neurons of the ganglion cell layer survived. Direct hypoxia from P3 caused hypertrophy of superficial vessels. Between P3 and P6, some vessels accelerated past the still-spreading astrocytes, often growing out of the retina into the vitreous humor. Direct hypoxia also caused astrocyte degeneration, but capillaries retained astrocyte investment and were not the site of vascular damage. By P8, breaches in the astrocytic glia limitans became prominent but were restricted to large veins. At such breaches, bleeding into the vitreous humor was common.
Retinal vessels normally develop in close association with astrocytes. Where that association is broken, preretinal vessels may grow or bleed into the vitreous humor. Astrocytes play important roles in constraining retinal vessels to the retina and in maintaining their integrity.
评估星形胶质细胞在控制发育中视网膜血管生长方面的作用。
在三种条件下检查新生大鼠视网膜中视网膜血管的生长情况：正常发育、周期性高氧和常氧（出生后第1天给予70%至75%氧气，之后1天给予室内空气，如此循环最多7次，然后持续给予室内空气最多16天），以及直接低氧（出生后第3天[P3]开始给予10%氧气）。将视网膜制成整装片，标记星形胶质细胞、小胶质细胞和血管，在一些实验中还检测凋亡特征性的DNA片段化情况。
在常氧条件下，视网膜浅层血管沿着星形胶质细胞的突起形成。在周期性高氧条件下，证实了其他人所描述的视网膜浅层血管减少及随后的新生血管形成。新生血管形成之前，星形胶质细胞群体因凋亡死亡而减少，首先是血管之间的星形胶质细胞减少，最终沿血管突破神经胶质界膜。最早的新生血管形成形式类似微动脉瘤，每个微动脉瘤通过毛细血管神经胶质界膜的缺陷突出。神经节细胞层的神经元存活。从P3开始的直接低氧导致浅层血管肥大。在P3和P6之间，一些血管加速生长，超过仍在扩展的星形胶质细胞，常常生长出视网膜进入玻璃体液。直接低氧还导致星形胶质细胞变性，但毛细血管仍保留星形胶质细胞的包绕，并非血管损伤的部位。到P – 8时，星形胶质神经胶质界膜的破裂变得明显，但仅限于大静脉。在这些破裂处，玻璃体液内出血很常见。
视网膜血管通常与星形胶质细胞密切相关地发育。当这种关联被破坏时，视网膜前血管可能生长或出血进入玻璃体液。星形胶质细胞在将视网膜血管限制在视网膜内并维持其完整性方面发挥着重要作用。
