The New England College of Optometry, 424 Beacon St., Boston, MA, USA.
The New England College of Optometry, 424 Beacon St., Boston, MA, USA.
Exp Eye Res. 2019 Apr;181:5-14. doi: 10.1016/j.exer.2019.01.008. Epub 2019 Jan 7.
Injections of the D2 dopamine receptor agonist quinpirole or the acetylcholine muscarinic receptor antagonists pirenzepine and atropine prevent the development of negative-lens-induced myopia in chicks by inhibiting ocular growth. Because ocular growth is diurnally rhythmic, we hypothesized that the efficacy for inhibition may depend on time of day. Chicks wore monocular -10D lenses for 5 days, starting at 12d of age. The light cycle was 12L/12D. The lens-wearing eye received daily intravitreal injections for 4 days, of 20 μl quinpirole (10 nmol), at the following times: 7:30 EST (lights-on; morning; n = 12), 12:00 (mid-day; n = 13), or 19:30 (evening; n = 17). The same protocol was used for pirenzepine (0.2 μmol) and atropine (18 nmol), at the following times: 8:30 EDT (lights-on; n = 10; n = 18), 14:00 (n = 10; n = 12), or 20:30 (n = 18; n = 16). Saline injections were done in separate groups of birds for all groups as controls, and the data combined (n = 28). Ocular dimensions were measured using A-scan ultrasonography on treatment day 1 at 12:00, and again on day 5 at 12:00; growth rate is defined as the change in axial length over 96 h. For quinpirole and pirenzepine, subsets (n's in Methods) of mid-day and evening groups were measured at 6 h intervals on day 5 (from 12:00 to 12:00) to obtain rhythm parameters for axial length and choroidal thickness; for atropine, only the mid-day group was measured. Refractions were measured on day 5 with a Hartinger's refractometer. For quinpirole and pirenzepine, mid-day injections were more effective at inhibiting ocular growth than evening (Exp-fellow: quinpirole: -68 vs 118 μm/96h; post-hoc Bonferroni p = 0.016; pirenzepine: 79 vs 215 μm/96h; p = 0.046). There were no between-group statistically significant differences for atropine. For quinpirole, the mid-day amplitude of the axial rhythm was smaller than for evening (95 vs 142 μm; p < 0.05), but there were no time-dependent effects on the rhythms for pirenzepine. For atropine, the amplitude of the axial-length rhythm was significantly larger than that for pirenzepine at mid-day. We conclude that there is a phase-dependent efficacy for quinpirole and pirenzepine, with mid-day injections being most effective. There were no consistent time-dependent alterations in rhythm parameters for any of the drugs.
D2 多巴胺受体激动剂喹吡罗或乙酰胆碱毒蕈碱受体拮抗剂哌仑西平和阿托品的注射可通过抑制眼球生长来预防负透镜诱导的小鸡近视的发展。由于眼球生长具有昼夜节律性，我们假设抑制作用的效果可能取决于一天中的时间。小鸡从 12 日龄开始佩戴 10D 单眼透镜 5 天。光周期为 12L/12D。佩戴透镜的眼睛每天接受 4 天的眼内注射，剂量为 20μl 喹吡罗（10nmol），时间如下：EST 7:30（开灯；早晨；n=12）、12:00（中午；n=13）或 19:30（晚上；n=17）。哌仑西平和阿托品（0.2μmol 和 18nmol）也采用相同的方案，时间如下：EDT 8:30（开灯；n=10；n=18）、14:00（n=10；n=12）或 20:30（n=18；n=16）。所有组别的鸟类都作为对照组进行了单独的盐水注射，数据合并（n=28）。在治疗第 1 天 12:00 进行眼部超声 A 扫描测量眼部尺寸，并在第 5 天 12:00 再次测量；生长速度定义为 96 小时内眼轴长度的变化。对于喹吡罗和哌仑西平，中午和晚上组的子集（方法中的 n）在第 5 天每隔 6 小时测量一次（从 12:00 到 12:00），以获得眼轴和脉络膜厚度的节律参数；对于阿托品，仅测量中午组。第 5 天使用 Hartinger 折射计测量屈光度。对于喹吡罗和哌仑西平，中午注射比晚上注射更能有效抑制眼球生长（Exp-fellow：喹吡罗：-68 对 118μm/96h；事后 Bonferroni p=0.016；哌仑西平：79 对 215μm/96h；p=0.046）。阿托品组之间没有统计学上的显著差异。对于喹吡罗，中午的眼轴节律幅度小于晚上（95 对 142μm；p<0.05），但哌仑西平的节律没有时间依赖性影响。对于阿托品，眼轴节律的幅度明显大于中午的哌仑西平。我们得出的结论是，喹吡罗和哌仑西平的疗效存在相位依赖性，中午注射效果最佳。任何药物的节律参数都没有一致的时间依赖性变化。
