Nathanson J A, McKee M
Department of Neurology, Harvard Medical School, Massachusetts, USA.
Invest Ophthalmol Vis Sci. 1995 Aug;36(9):1765-73.
Nitric oxide (NO) is an important intracellular and intercellular regulator in nerve tissue as well as in vascular endothelium, smooth muscle, and certain other cell types. In the ocular anterior segment, studies in rat have revealed a comparatively restricted distribution of the NO synthetic enzyme, NO synthase (NOS-1). Recent physiological studies, however, have shown that NO-mimicking nitrovasodilators can alter intraocular pressure in monkeys through an action (at least in part) on outflow resistance. The current studies, which determine the sites of NO synthesis in the human outflow pathway, were performed to provide an anatomic and biochemical explanation for these observations.
The occurrence and distribution of sites of ocular NO production in postmortem human eyes were determined using the isozyme-independent NO-indicator marker, NADPH-diaphorase (NADPH-d), together with direct biochemical assay and immunocytochemical localization of specific NO synthase (NOS) isoforms.
The ciliary muscle (CM) and outflow pathway of normal human eyes were found to be substantially enriched in NADPH-d, the majority of which, by immunological analysis, consisted not of NOS-1 (brain or bNOS) but rather of NOS type 3 (endothelial cell or ecNOS). Biochemical analysis confirmed the NADPH-dependent production of NO and, unlike the primarily soluble distribution of bNOS, activity was found in both particulate and soluble fractions. NO reactivity was enriched in major sites of outflow resistance (trabecular meshwork and Schlemm's canal) as well as in collecting channels and was particularly prominent in the CM, especially in the anatomically distinct longitudinal subgroup of CM fibers that insert near (and may normally play a role in regulating resistance in) the trabecular meshwork.
The human outflow pathway and CM are enriched sites of NO synthesis. These sites are anatomically distributed in such a manner as to suggest that one possible role for NO in the anterior segment may be to modulate outflow resistance either directly at the level of the trabecular meshwork, Schlemm's canal and collecting channels, or indirectly through alteration in the tone of the longitudinal CM.
一氧化氮（NO）是神经组织以及血管内皮、平滑肌和某些其他细胞类型中重要的细胞内和细胞间调节剂。在眼前节，对大鼠的研究显示一氧化氮合成酶（NOS-1）的分布相对受限。然而，最近的生理学研究表明，模拟NO的硝基血管扩张剂可通过（至少部分地）作用于房水流出阻力来改变猴子的眼压。进行当前这些确定人类房水流出途径中NO合成部位的研究，旨在为这些观察结果提供解剖学和生物化学解释。
使用不依赖同工酶的NO指示剂标记物烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d），结合直接生化测定和特定一氧化氮合酶（NOS）同工型的免疫细胞化学定位，来确定死后人类眼睛中眼内NO产生部位的发生情况和分布。
发现正常人眼的睫状肌（CM）和房水流出途径中NADPH-d大量富集，通过免疫分析，其中大部分不是由NOS-1（脑型或bNOS）组成，而是由3型NOS（内皮细胞型或ecNOS）组成。生化分析证实了NO的NADPH依赖性产生，并且与bNOS主要为可溶性分布不同，在颗粒和可溶部分均发现了活性。NO反应性在主要的房水流出阻力部位（小梁网和施莱姆管）以及集合管中富集，在CM中尤为突出，特别是在插入小梁网附近（并且可能通常在调节阻力中起作用）的解剖学上不同的CM纤维纵向亚组中。
人类房水流出途径和CM是NO合成的富集部位。这些部位在解剖学上的分布方式表明，NO在眼前节的一个可能作用可能是直接在小梁网、施莱姆管和集合管水平调节房水流出阻力，或者通过改变纵向CM的张力间接调节。
