Low nitric oxide synthases (NOSs) in eyes with age-related macular degeneration (AMD).

Low nitric oxide synthases (NOSs) in eyes with age-related macular degeneration (AMD).
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DOI:
10.1016/j.exer.2009.10.004
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发表时间:
2010-01
影响因子:
3.4
通讯作者:
Lutty, Gerard A.
Lutty, Gerard A.
中科院分区:
医学3区
文献类型:
--
作者:
Bhutto, Imran A.;Baba, Takayuki;Merges, Carol;McLeod, D. Scott;Lutty, Gerard A.

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血管内皮细胞产生的一氧化氮(NO)在血流调节中是重要的。NO的产生减少会对血流和其他血管功能产生不利影响。我们研究了三种一氧化氮合酶(NOS)亚型在老年人和AMD患者视网膜和脉络膜中的表达。碱性磷酸酶免疫组织化学进行诱导型(iNOS),神经元(nNOS),内皮细胞(eNOS)的NOS的抗体冷冻保存的部分从老年对照供体眼睛(n= 13)和眼睛与AMD(n= 22)。CD34抗体用作内皮细胞(EC)标记物。三名独立的蒙面观察员对免疫组织化学反应产物的强度进行评分。对老年对照眼和AMD眼的平均评分进行统计学比较。在老年对照组,nNOS在神经节细胞(RGCs)和两个核层的神经元。脉络膜中血管周围神经纤维和视网膜色素上皮细胞nNOS阳性。eNOS和iNOS仅限于视网膜和脉络膜血管内皮细胞。脉络膜中的一些细胞(推测为黑素细胞或树突状细胞)也呈eNOS阳性。在AMD眼中,与老年对照眼相比,RGCs、神经元、视网膜血管和RPE中的nNOS显著降低(p≤0.05)。iNOS和eNOS在老年对照和AMD眼之间没有显着差异,除了AMD眼的脉络膜动脉(p=0.006)和脉络膜细胞(p=0.03)中的eNOS显着减少。虽然没有直接测量NO,但这些发现表明AMD眼睛中产生的NO较少。AMD患者视网膜nNOS的减少可能与神经元变性有关。AMD脉络膜中nNOS和eNOS的减少可能与血管收缩和血流动力学改变有关。
Nitric oxide (NO) production by vascular endothelium is important in regulation of blood flow. Reduced production of NO can adversely affect blood flow and other vascular functions. We investigated the expression of three nitric oxide synthase (NOS) isoforms in retina and choroid of aged human eyes and eyes with AMD. Alkaline phosphatase immunohistochemistry was performed using antibodies against inducible (iNOS), neuronal (nNOS), and endothelial (eNOS) NOSs on cryopreserved sections from aged control donor eyes (n= 13) and eyes with AMD (n= 22). CD34 antibody was used as an endothelial cell (EC) marker. Three independent masked observers scored the intensity of the immunohistochemical reaction product. Mean scores from the aged control and AMD eyes were statistically compared. In aged control retinas, nNOS was in ganglion cells (RGCs) and neurons of both nuclear layers. In choroid, perivascular nerve fibers and retinal pigment epithelial (RPE) cells were nNOS+. eNOS and iNOS were confined to the retinal and choroidal vascular ECs. Some cells presumably melanocytes or dendritic cells in choroid were also eNOS+. In AMD eyes, nNOS was significantly lower in RGCs, neurons, retinal vessels and RPE (p≤0.05) compared to the aged control eyes. iNOS and eNOS showed no significant differences between aged control and AMD eyes except that there was significantly less eNOS in choroidal arteries (p=0.006) and choroidal cells (p=0.03) of AMD eyes. Although NO was not measured directly, these findings suggest that there is less NO produced in AMD eyes. The decrease in retinal nNOS in AMD eyes is probably related to neuronal degeneration. The decrease in nNOS and eNOS in AMD choroid could be associated with vasoconstriction and hemodynamic changes.
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