Ophthalmic Research Institute, University of Tuebingen, Tuebingen, Germany.
Institute for Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
Graefes Arch Clin Exp Ophthalmol. 2023 Feb;261(2):409-425. doi: 10.1007/s00417-022-05837-w. Epub 2022 Oct 4.
Recently, an increasing number of studies relied on the assumption that visually induced changes in choroidal thickness can serve as a proxy to predict future axial eye growth. The retinal signals controlling choroidal thickness are, however, not well defined. We have studied the potential roles of dopamine, released from the retina, in the choroidal response in the chicken.
Changes in retinal dopamine release and choroidal thickness changes were induced by intravitreal injections of either atropine (250 µg or 360 nMol), atropine combined with a dopamine antagonist, spiperone (500 µMol), or spiperone alone and were tracked by optical coherence tomography (OCT). To visually stimulate dopamine release, other chicks were exposed to flicker light of 1, 10, or 400 Hz (duty cycle 0.2) and choroidal thickness was tracked. In all experiments, dopamine and 3,4-Dihydroxyphenylacetic acid (DOPAC) were measured in vitreous, retina, and choroid by high-performance liquid chromatography with electrochemical detection (HLPC-ED). The distribution of the rate-limiting enzyme of dopamine synthesis, tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), vascular endothelial growth factor (VEGF), and alpha2A adrenoreceptors (alpha2A-ADR) was studied in the choroid by immunofluorescence.
The choroid thickened strongly in atropine-injected eyes, less so in atropine + spiperone-injected eyes and became thinner over the day in spiperone alone-, vehicle-, or non-injected eyes. Flickering light at 20 lx, both 1 and 10 Hz, prevented diurnal choroidal thinning, compared to 400 Hz, and stimulated retinal dopamine release. Correlation analysis showed that the higher retinal dopamine levels or release, the thicker became the choroid. TH-, nNOS-, VEGF-, and alpha2A adrenoreceptor-positive nerve fibers were localized in the choroid around lacunae and in the walls of blood vessels with colocalization of TH and nNOS, and TH and VEGF.
Retinal DOPAC and dopamine levels were positively correlated with choroidal thickness. TH-positive nerve fibers in the choroid were closely associated with peptides known to play a role in myopia development. Findings are in line with the hypothesis that dopamine is related to retinal signals controlling choroidal thickness.
最近,越来越多的研究依赖于这样一种假设,即脉络膜厚度的视觉诱导变化可以作为预测未来眼球轴向生长的替代物。然而,控制脉络膜厚度的视网膜信号还没有得到很好的定义。我们研究了从视网膜释放的多巴胺在鸡的脉络膜反应中的潜在作用。
通过玻璃体内注射阿托品(250μg 或 360nMol)、阿托品与多巴胺拮抗剂哌啶(500μMol)或单独哌啶,诱导视网膜多巴胺释放和脉络膜厚度变化,并通过光学相干断层扫描(OCT)进行跟踪。为了视觉刺激多巴胺释放,其他小鸡暴露于 1、10 或 400Hz 的闪烁光(占空比 0.2)并跟踪脉络膜厚度。在所有实验中,通过高效液相色谱电化学检测(HLPC-ED)测量玻璃体内、视网膜和脉络膜中的多巴胺和 3,4-二羟苯乙酸(DOPAC)。通过免疫荧光研究脉络膜中多巴胺合成限速酶酪氨酸羟化酶(TH)、神经元型一氧化氮合酶(nNOS)、血管内皮生长因子(VEGF)和α2A 肾上腺素能受体(α2A-ADR)的分布。
阿托品注射眼的脉络膜明显增厚,阿托品+哌啶注射眼的脉络膜增厚较少,而哌啶、载体或未注射眼的脉络膜在一天中变薄。与 400Hz 相比,20lx 的闪烁光(1Hz 和 10Hz)可防止日间脉络膜变薄,并刺激视网膜多巴胺释放。相关分析表明,视网膜多巴胺水平或释放越高,脉络膜越厚。TH-、nNOS-、VEGF-和α2A 肾上腺素能受体阳性神经纤维定位于脉络膜周围的腔隙和血管壁中,TH 和 nNOS、TH 和 VEGF 共定位。
视网膜 DOPAC 和多巴胺水平与脉络膜厚度呈正相关。脉络膜中的 TH 阳性神经纤维与已知在近视发展中起作用的肽密切相关。这些发现与多巴胺与控制脉络膜厚度的视网膜信号有关的假设一致。