Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Australia.
Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Australia.
Exp Eye Res. 2020 Nov;200:108233. doi: 10.1016/j.exer.2020.108233. Epub 2020 Sep 10.
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.
Dopamine or deuterated dopamine (Dopamine-1,1,2,2-d 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.
Both intravitreal (ED = 0.002μmoles) and topical application (ED = 6.10μmoles) 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).
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.
动物模型表明,视网膜多巴胺系统的失调与实验性近视(近视)的发展之间存在关联。然而,动物模型中多巴胺的药理学研究严重依赖于玻璃体内或全身给药,这对长期实验有几个限制。因此,我们研究了多巴胺作为局部滴眼剂给药是否可以抑制小鸡形觉剥夺性近视(FDM)的发展。我们还研究了通过氘取代对多巴胺进行化学修饰是否可以提高多巴胺的稳定性和生物利用度,从而在局部给药时增加多巴胺对抗 FDM 的有效性。
多巴胺或氘代多巴胺(Dopamine-1,1,2,2-d 盐酸盐)以递增剂量范围(每组至少 n = 6)每天通过玻璃体内注射或局部滴眼剂给药给正在发展 FDM 的小鸡。在治疗 4 天后测量眼轴长度和屈光度。
玻璃体内(ED = 0.002μmoles)和局部应用(ED = 6.10μmoles)多巴胺均以剂量依赖性方式抑制 FDM 的发展。然而,玻璃体内注射引起的保护作用明显高于局部滴眼剂(p < 0.01)。氘代多巴胺作为玻璃体内注射(p = 0.897)或局部滴眼剂(p = 0.921)给药时,对 FDM 的抑制作用与未修饰的多巴胺相似。
玻璃体内和局部应用多巴胺均以剂量依赖性方式抑制 FDM 的发展,表明局部给药可能是进行长期多巴胺实验的有效途径。氘取代不会改变多巴胺作为玻璃体内注射或局部滴眼剂给药时对 FDM 的保护作用。