Huxlin K R, Bennett M R
Department of Physiology, University of Sydney, NSW, Australia.
Eur J Neurosci. 1995 Nov 1;7(11):2226-39. doi: 10.1111/j.1460-9568.1995.tb00644.x.
The large majority of mammalian retinal ganglion cells degenerate following section of their axons in the optic nerve. It has been suggested that some axotomized retina ganglion cells die because of toxic agents produced within their immediate environment. Our hypothesis was that nitric oxide might be one of the toxic factors implicated in the death of adult retinal ganglion cells post-axotomy. In the first instance, we determined whether there were any changes in the retinal expression of NADPH diaphorase both 3 and 14 days following intraorbital section of the optic nerve in adult rats. Secondly, if nitric oxide was indeed implicated in the death of ganglion cells, then trophic factors which rescue these neurons might do so by decreasing the expression of nitric oxide synthase. Recently, we found that a collicular proteoglycan purified from the major target of retinal ganglion cells, the superior colliculus, rescued a greater proportion of adult ganglion cells from axotomy-induced death than most other known trophic factors. We thus injected this proteoglycan intraocularly after section of the optic nerve and examined its effect on the expression of NADPH diaphorase in the retina. Thirdly, an inhibitor of nitric oxide synthetase was repeatedly injected into the eye following the section of the optic nerve in order to determine if such a treatment might improve the survival of retinal ganglion cells. The present results indicate that section of the optic nerve does not alter the overall levels of NADPH diaphorase within the adult rat retina. Intraocular injections of the collicular proteoglycan actually increased the number of neurons expressing NADPH diaphorase, particularly in the ganglion cell layer. Finally, inhibition of nitric oxide synthetase following axotomy resulted in increased loss of retinal ganglion cells over a 2 week period when compared with controls. Our findings indicate that, rather than being toxic, small amounts of nitric oxide may be important for the survival of a proportion of injured retina ganglion cells.
大多数哺乳动物的视网膜神经节细胞在其轴突于视神经中被切断后会发生退化。有人提出，一些轴突被切断的视网膜神经节细胞死亡是由于其周围环境中产生的有毒物质所致。我们的假设是，一氧化氮可能是成年视网膜神经节细胞轴突切断后死亡所涉及的有毒因素之一。首先，我们确定在成年大鼠眶内切断视神经后3天和14天，视网膜中NADPH黄递酶的表达是否有任何变化。其次，如果一氧化氮确实与神经节细胞的死亡有关，那么挽救这些神经元的营养因子可能通过降低一氧化氮合酶的表达来实现。最近，我们发现从视网膜神经节细胞的主要靶标上丘中纯化出的一种上丘蛋白聚糖，比大多数其他已知的营养因子能挽救更大比例的成年神经节细胞免于轴突切断诱导的死亡。因此，我们在切断视神经后将这种蛋白聚糖眼内注射，并检查其对视网膜中NADPH黄递酶表达的影响。第三，在切断视神经后反复向眼内注射一氧化氮合酶抑制剂，以确定这种治疗是否可能改善视网膜神经节细胞的存活。目前的结果表明，切断视神经不会改变成年大鼠视网膜内NADPH黄递酶的总体水平。眼内注射上丘蛋白聚糖实际上增加了表达NADPH黄递酶的神经元数量，尤其是在神经节细胞层。最后，与对照组相比，轴突切断后抑制一氧化氮合酶导致在2周内视网膜神经节细胞的损失增加。我们的研究结果表明，少量的一氧化氮可能对一部分受损视网膜神经节细胞的存活很重要，而不是有毒。
