Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model.
Inducible nitric oxide synthase, Nos2, does not mediate optic neuropathy and retinopathy in the DBA/2J glaucoma model.
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DOI：
10.1186/1471-2202-8-108
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发表时间：
2007-12-19
期刊：
影响因子：
2.4
通讯作者：
John SW
中科院分区：
文献类型：
--
作者：
Libby RT;Howell GR;Pang IH;Savinova OV;Mehalow AK;Barter JW;Smith RS;Clark AF;John SW
一氧化氮合酶2（NOS 2）在某些情况下有助于神经死亡，但其在青光眼中的作用仍有争议。在通过血管烧灼实验性升高眼内压（IOP）的大鼠青光眼模型中，NOS 2与视网膜神经节细胞变性有关，但在通过注射高渗盐水升高IOP的大鼠青光眼模型中，NOS 2与视网膜神经节细胞变性无关。为了测试NOS 2对遗传性青光眼的重要性，在这项研究中，我们在DBA/2 J小鼠青光眼模型中遗传性地和非遗传性地降低NOS 2活性。在疾病发病的不同阶段，在RNA和蛋白质水平上分析了Nos 2在视神经乳头中的表达。为了测试Nos 2在青光眼性神经变性中的参与，将Nos 2的无效等位基因回交到DBA/2 J小鼠中，并在每个Nos 2基因型的小鼠中评估青光眼的发病率和严重程度。此外，DBA/2 J小鼠用NOS 2抑制剂氨基胍治疗，并与未治疗的小鼠进行比较。视神经乳头Nos 2 RNA水平变化，在中度增加，但在早期和严重阶段的疾病下降。尽管在视乳头中存在少量NOS 2阳性细胞，但在青光眼期间NOS 2蛋白并没有显著增加。Nos 2或氨基胍治疗的遗传缺陷没有改变DBA/2 J小鼠的IOP曲线。此外，无论是Nos 2缺乏症，也没有氨基胍有任何可检测到的影响，视神经损伤。DBA/2 J小鼠的青光眼性神经变性不需要NOS 2活性。需要进一步的实验涉及各种模型，以评估Nos 2在青光眼中的普遍重要性。
Nitric oxide synthase 2 (NOS2) contributes to neural death in some settings, but its role in glaucoma remains controversial. NOS2 is implicated in retinal ganglion cell degeneration in a rat glaucoma model in which intraocular pressure (IOP) is experimentally elevated by blood vessel cauterization, but not in a rat glaucoma model where IOP was elevated by injection of hypertonic saline. To test the importance of NOS2 for an inherited glaucoma, in this study we both genetically and pharmacologically decreased NOS2 activity in the DBA/2J mouse glaucoma model. The expression of Nos2 in the optic nerve head was analyzed at both the RNA and protein levels at different stages of disease pathogenesis. To test the involvement of Nos2 in glaucomatous neurodegeneration, a null allele of Nos2 was backcrossed into DBA/2J mice and the incidence and severity of glaucoma was assessed in mice of each Nos2 genotype. Additionally, DBA/2J mice were treated with the NOS2 inhibitor aminoguanidine and the disease compared to untreated mice. Optic nerve head Nos2 RNA levels varied and increased during moderate but decreased at early and severe stages of disease. Despite the presence of a few NOS2 positive cells in the optic nerve head, NOS2 protein was not substantially increased during the glaucoma. Genetic deficiency of Nos2 or aminoguanidine treatment did not alter the IOP profile of DBA/2J mice. Additionally, neither Nos2 deficiency nor aminoguanidine had any detectable affect on the glaucomatous optic nerve damage. Glaucomatous neurodegeneration in DBA/2J mice does not require NOS2 activity. Further experiments involving various models are needed to assess the general importance of Nos2 in glaucoma.
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影响因子：
--
作者：
ARMALY, MF;KRUEGER, DE;SHAFFER, RN
通讯作者：
SHAFFER, RN
影响因子：
5.1
作者：
Anderson, DR
通讯作者：
Anderson, DR
视网膜神经节细胞变性是拓扑的，但在DBA/2J小鼠中不是特异性细胞类型。
影响因子：
7.8
作者：
Jakobs, Tatjana C;Libby, Richard T;Ben, Yixin;John, Simon W M;Masland, Richard H
通讯作者：
Masland, Richard H
DOI：
10.1073/pnas.92.23.10688
发表时间：
1995-11-07
影响因子：
11.1
作者：
LAUBACH, VE;SHESELY, EG;SHERMAN, PA
通讯作者：
SHERMAN, PA
影响因子：
30.8
作者：
Anderson, MG;Smith, RS;John, SWM
通讯作者：
John, SWM