Purpose

Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the development of experimental myopia (short-sightedness). However, pharmacological investigations of dopamine in animal models rely heavily on intravitreal or systemic administration, which have several limitations for longer-term experiments. We therefore investigated whether administration of dopamine as a topical eye drop can inhibit the development of form-deprivation myopia (FDM) in chicks. We also examined whether chemical modification of dopamine through deuterium substitution, which might enhance stability and bioavailability, can increase dopamine's effectiveness against FDM when given topically.

Methods

Dopamine or deuterated dopamine (Dopamine-1,1,2,2-d₄ hydrochloride) was administered as a daily intravitreal injection or as daily topical eye drops to chicks developing FDM over an ascending dose range (min. n = 6 per group). Axial length and refraction were measured following 4 days of treatment.

Results

Both intravitreal (EC₅₀ = 0.002mmoles) and topical application (EC₅₀ = 6.10mmoles) of dopamine inhibited the development of FDM in a dose-dependent manner. Intravitreal injections, however, elicited a significantly higher level of protection relative to topical eye drops (p < 0.01). Deuterated dopamine inhibited FDM to a similar extent as unmodified dopamine when administered as intravitreal injections (p = 0.897) or topical eye drops (p = 0.921).

Conclusions

Both intravitreal and topical application of dopamine inhibit the development of FDM in a dose-dependent manner, indicating that topical administration may be an effective avenue for longer-term dopamine experiments. Deuterium substitution does not alter the protection afforded by dopamine against FDM when given as either an intravitreal injection or topical eye drop.

中文翻译：

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多巴胺能化合物的局部应用可以抑制雏鸡的剥夺性近视。

目的

动物模型已证明，视网膜多巴胺系统失调与实验性近视的发展（近视）之间存在联系。但是，在动物模型中对多巴胺进行的药理研究在很大程度上依赖于玻璃体内或全身给药，这对长期实验具有一些局限性。因此，我们研究了将多巴胺作为局部滴眼剂给药是否可以抑制雏鸡形成性剥夺性近视（FDM）的发展。我们还研究了局部给药时，通过氘代进行的多巴胺化学修饰是否可能增强稳定性和生物利用度，从而可以提高多巴胺对抗FDM的有效性。

方法

多巴胺或氘代多巴胺（多巴胺-1,1,2,2-d ₄盐酸盐）以每日玻璃体内注射方式或以局部滴眼剂的形式向在递增剂量范围内发展为FDM的雏鸡给药（每组最低n = 6） 。治疗4天后测量轴长和屈光度。

结果

玻璃体内（EC ₅₀  = 0.002mmoles）和局部应用（EC ₅₀  = 6.10mmoles）多巴胺均以剂量依赖的方式抑制FDM的发展。然而，与局部滴眼液相比，玻璃体内注射引起的保护水平明显更高（p <0.01）。当以玻璃体内注射（p = 0.897）或局部滴眼液（p = 0.921）给药时，氘代多巴胺对FDM的抑制程度与未修饰的多巴胺相似。

结论

玻璃体内和局部应用多巴胺都以剂量依赖的方式抑制FDM的发展，表明局部给药可能是长期多巴胺实验的有效途径。当以玻璃体内注射或局部滴眼剂给药时，氘取代不会改变多巴胺对FDM的保护作用。