Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Canberra, Australia.
Research School of Biology, Australian National University, Canberra, Australia.
Invest Ophthalmol Vis Sci. 2021 Apr 1;62(4):25. doi: 10.1167/iovs.62.4.25.
Topical application of levodopa inhibits the development of form-deprivation myopia (FDM) and lens-induced myopia (LIM) in chicks. Here we examine whether coadministration with carbidopa enhances this protection and compare the effectiveness of topical versus systemic administration. We also investigate the degree to which topical and systemic administration of these compounds alters retinal dopamine release and examine whether this is the mechanism by which they inhibit experimental myopia.
Levodopa and levodopa:carbidopa (at a 4:1 ratio) were administered as twice-daily eye drops or once-daily intraperitoneal injections to chicks developing FDM or LIM over an ascending dose range. Axial length and refraction were measured following 4 days of treatment. Dopamine levels in the vitreous and blood were analyzed using liquid chromatography-mass spectrometry following topical or systemic administration of levodopa or levodopa:carbidopa. Finally, chicks receiving topical or systemic levodopa or levodopa:carbidopa were cotreated with the dopamine antagonist spiperone.
Levodopa:carbidopa inhibited the development of FDM and LIM to a greater extent than levodopa alone (P < 0.05). Topical application was more effective than systemic administration (P < 0.001). Vitreal dopamine levels were increased to the greatest extent by topical application of levodopa:carbidopa (P < 0.001). Systemic but not topical administration significantly increased dopamine levels within the blood (P < 0.01). Cotreatment with spiperone inhibited the antimyopic effects (P < 0.05) of levodopa and levodopa:carbidopa.
The presence of carbidopa increases the bioavailability of levodopa within the eye, enhancing its antimyopic effects, with topical application showing the greatest efficacy. Thus levodopa:carbidopa may be a promising treatment for controlling the progression of human myopia.
局部应用左旋多巴可抑制形觉剥夺性近视（FDM）和晶状体诱导性近视（LIM）在小鸡中的发展。在这里，我们检查卡比多巴是否能增强这种保护作用，并比较局部和全身给药的效果。我们还研究了这些化合物的局部和全身给药改变视网膜多巴胺释放的程度，并检查这是否是它们抑制实验性近视的机制。
左旋多巴和左旋多巴：卡比多巴（4:1 比例）以每日两次滴眼或每日一次腹腔注射的方式给予正在形成 FDM 或 LIM 的小鸡，剂量逐渐增加。治疗 4 天后测量眼轴长度和屈光度。用液相色谱-质谱法分析玻璃体和血液中的多巴胺水平，然后给予局部或全身左旋多巴或左旋多巴：卡比多巴。最后，接受局部或全身左旋多巴或左旋多巴：卡比多巴治疗的小鸡用多巴胺拮抗剂三氟拉嗪进行共同治疗。
左旋多巴：卡比多巴抑制 FDM 和 LIM 的发展比单独使用左旋多巴更有效（P < 0.05）。局部应用比全身给药更有效（P < 0.001）。局部应用左旋多巴：卡比多巴可使玻璃体多巴胺水平升高到最大程度（P < 0.001）。系统但不是局部给药可使血液内多巴胺水平显著升高（P < 0.01）。三氟拉嗪共同治疗抑制了左旋多巴和左旋多巴：卡比多巴的抗近视作用（P < 0.05）。
卡比多巴的存在增加了左旋多巴在眼睛内的生物利用度，增强了其抗近视作用，局部应用的效果最好。因此，左旋多巴：卡比多巴可能是控制人类近视进展的一种有前途的治疗方法。
