Huang Yao, Li Zhiwei, van Rooijen Nico, Wang Ningli, Pang Chi Pui, Cui Qi
Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The Chinese University of Hong Kong, 147K Argyle Street, Kowloon, Hong Kong, PR China.
Exp Eye Res. 2007 Nov;85(5):659-66. doi: 10.1016/j.exer.2007.07.020. Epub 2007 Aug 6.
Recently macrophages were shown to play a protective role in retinal ganglion cells (RGCs) after optic nerve (ON) injury. In the present study, we investigated how macrophages responded after acute intraocular pressure (IOP) elevation in experimental autoimmune encephalomyelitis (EAE)-resistant Fischer 344 (F344) and Sprague Dawley (SD) rats and EAE-vulnerable Lewis rats. Acute IOP elevation was performed at 110mmHg for 2h to mimic acute glaucoma. Phagocytic cells in the eye were removed by intravitreal application of clodronate liposomes whereas macrophage activation was achieved by intravitreal injection of zymosan, a yeast wall preparation. Fluorescence dye, FluoroGold, was applied behind the eyeballs to retrogradely label surviving RGCs 40h before animal sacrifice. Macrophages in the retina were identified by ED1 immunostaining. Loss of 25% RGCs in F344 but over 90% in Lewis rats was seen 2 weeks after acute IOP elevation. Significant increase in the number of macrophages in the retina was seen to accompany the great RGC loss in Lewis rats; removal of these macrophages reduced the extent of RGC loss, suggesting the involvement of macrophages in RGC death in Lewis strain. Low numbers of macrophages were seen in F344 retinas after acute IOP elevation, and removal of macrophages did not show clear effect on RGC viability. Whereas macrophage activation by zymosan protected RGCs after ON axotomy in F344 rats, the same macrophage activation became detrimental to RGCs after acute IOP elevation. The extent of RGC loss 3 weeks after acute IOP elevation or after macrophage activation by zymosan in EAE-resistant SD rats was similar to that in F344 rats. We thus demonstrate that macrophages in rats with different autoimmune backgrounds react differently to acute IOP elevation and differentially modulate RGC loss, a phenomenon contrary to the protective action in RGCs after ON axotomy. These data suggest that autoimmune background plays a role in modulating vulnerability of RGCs to acute IOP elevation.
最近研究表明，巨噬细胞在视神经（ON）损伤后对视网膜神经节细胞（RGCs）起到保护作用。在本研究中，我们调查了实验性自身免疫性脑脊髓炎（EAE）抗性的Fischer 344（F344）大鼠、Sprague Dawley（SD）大鼠以及EAE易感性Lewis大鼠在急性眼压（IOP）升高后巨噬细胞的反应。通过将眼压升至110mmHg并维持2小时来模拟急性青光眼，从而实现急性IOP升高。通过玻璃体内注射氯膦酸盐脂质体清除眼中的吞噬细胞，而通过玻璃体内注射酵母聚糖（一种酵母细胞壁制剂）来激活巨噬细胞。在动物处死前40小时，将荧光染料FluoroGold应用于眼球后方，以逆行标记存活的RGCs。通过ED1免疫染色鉴定视网膜中的巨噬细胞。急性IOP升高2周后，F344大鼠中有25%的RGCs丢失，而Lewis大鼠中超过90%的RGCs丢失。在Lewis大鼠中，随着大量RGCs丢失，视网膜中巨噬细胞数量显著增加；清除这些巨噬细胞可减少RGCs丢失的程度，这表明巨噬细胞参与了Lewis品系中RGCs的死亡。急性IOP升高后，在F344大鼠视网膜中可见少量巨噬细胞，清除巨噬细胞对RGCs活力未显示出明显影响。虽然酵母聚糖激活巨噬细胞在F344大鼠ON轴突切断后对RGCs有保护作用，但在急性IOP升高后，相同的巨噬细胞激活对RGCs却有害。急性IOP升高3周后或在EAE抗性SD大鼠中经酵母聚糖激活巨噬细胞后，RGCs丢失的程度与F344大鼠相似。因此，我们证明具有不同自身免疫背景的大鼠巨噬细胞对急性IOP升高的反应不同，并对RGCs丢失有不同的调节作用，这一现象与ON轴突切断后巨噬细胞对RGCs的保护作用相反。这些数据表明，自身免疫背景在调节RGCs对急性IOP升高的易感性中起作用。
