Carr Brittany J, Stell William K
Neuroscience Graduate Program, Snyder Institute for Chronic Diseases, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, Calgary, Alberta, Canada.
Department of Cell Biology and Anatomy and Department of Surgery; Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Sci Rep. 2016 Dec 5;6(1):9. doi: 10.1038/s41598-016-0002-7.
Myopia is the most common childhood refractive disorder. Atropine inhibits myopia progression, but its mechanism is unknown. Here, we show that myopia-prevention by atropine requires production of nitric oxide (NO). Form-deprivation myopia (FDM) was induced in week-old chicks by diffusers over the right eye (OD); the left eye (OS) remained ungoggled. On post-goggling days 1, 3, and 5, OD received intravitreally 20 µL of phosphate-buffered saline (vehicle), or vehicle plus: NO source: L-arginine (L-Arg, 60-6,000 nmol) or sodium nitroprusside (SNP, 10-1,000 nmol); atropine (240 nmol); NO inhibitors: L-NIO or L-NMMA (6 nmol); negative controls: D-Arg (10 µmol) or D-NMMA (6 nmol); or atropine plus L-NIO, L-NMMA, or D-NMMA; OS received vehicle. On day 6 post-goggling, refractive error, axial length, equatorial diameter, and wet weight were measured. Vehicle-injected goggled eyes developed significant FDM. This was inhibited by L-Arg (ED50 = 400 nmol) or SNP (ED50 = 20 nmol), but not D-Arg. Higher-dose SNP, but not L-Arg, was toxic to retina/RPE. Atropine inhibited FDM as expected; adding NOS-inhibitors (L-NIO, L-NMMA) to atropine inhibited this effect dose-dependently, but adding D-NMMA did not. Equatorial diameter, wet weight, and metrics of control eyes were not affected by any treatment. In summary, intraocular NO inhibits myopia dose-dependently and is obligatory for inhibition of myopia by atropine.
近视是最常见的儿童屈光不正疾病。阿托品可抑制近视进展，但其机制尚不清楚。在此，我们表明阿托品预防近视需要一氧化氮（NO）的产生。通过在一周龄雏鸡的右眼（OD）上方放置扩散器诱导形觉剥夺性近视（FDM）；左眼（OS）不戴眼罩。在戴眼罩后的第1、3和5天，OD眼玻璃体内注射20µL磷酸盐缓冲盐水（载体），或载体加：NO供体：L-精氨酸（L-Arg，60 - 6000 nmol）或硝普钠（SNP，10 - 1000 nmol）；阿托品（240 nmol）；NO抑制剂：L-NIO或L-NMMA（6 nmol）；阴性对照：D-精氨酸（10µmol）或D-NMMA（6 nmol）；或阿托品加L-NIO、L-NMMA或D-NMMA；OS眼注射载体。在戴眼罩后的第6天，测量屈光不正、眼轴长度、赤道直径和湿重。注射载体的戴眼罩眼出现了明显的FDM。这被L-Arg（半数有效剂量[ED50]=400 nmol）或SNP（ED50 = 20 nmol）抑制，但D-Arg无此作用。高剂量的SNP对视网膜/视网膜色素上皮有毒性，但L-Arg无此作用。阿托品如预期那样抑制了FDM；在阿托品中加入一氧化氮合酶抑制剂（L-NIO、L-NMMA）可剂量依赖性地抑制这种作用，但加入D-NMMA则无此作用。任何处理均未影响对照眼的赤道直径、湿重和其他指标。总之，眼内NO剂量依赖性地抑制近视，并且是阿托品抑制近视所必需的。
