Department of Ophthalmology, Boston Children's Hospital, Boston, Massachusetts.
Invest Ophthalmol Vis Sci. 2013 Dec 19;54(13):8275-84. doi: 10.1167/iovs.13-12544.
Dopamine (DA) is a neurotransmitter implicated both in modulating neural retinal signals and in eye growth. Therefore, it may participate in the pathogenesis of the most common clinical sequelae of retinopathy of prematurity (ROP), visual dysfunction and myopia. Paradoxically, in ROP myopia the eye is usually small. The eye of the rat with oxygen-induced retinopathy (OIR) is characterized by retinal dysfunction and short axial length. There have been several investigations of the early maturation of DA in rat retina, but little at older ages, and not in the OIR rat. Therefore, DA, retinal function, and refractive state were investigated in the OIR rat.
In one set of rats, the development of dopaminergic (DAergic) networks was evaluated in retinal cross-sections from rats aged 14 to 120 days using antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in the biosynthesis of DA). In another set of rats, retinoscopy was used to evaluate spherical equivalent (SE), electoretinography (ERG) was used to evaluate retinal function, and high-pressure liquid chromatography (HPLC) was used to evaluate retinal contents of DA, its precursor levodopamine (DOPA), and its primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC).
The normally rapid postnatal ramification of DAergic neurons was disrupted in OIR rats. Retinoscopy revealed that OIR rats were relatively myopic. In the same eyes, ERG confirmed retinal dysfunction in OIR. HPLC of those eyes' retinae confirmed low DA. Regression analysis indicated that DA metabolism (evaluated by the ratio of DOPAC to DA) was an important additional predictor of myopia beyond OIR.
The OIR rat is the first known animal model of myopia in which the eye is smaller than normal. Dopamine may modulate, or fail to modulate, neural activity in the OIR eye, and thus contribute to this peculiar myopia.
多巴胺（DA）既是神经视网膜信号调节因子，也是眼球生长因子。因此，它可能参与了早产儿视网膜病变（ROP）最常见的临床后遗症，如视觉功能障碍和近视的发病机制。矛盾的是，ROP 患者的眼球通常较小。氧诱导的视网膜病变（OIR）大鼠的眼睛以视网膜功能障碍和眼轴短为特征。人们已经对大鼠视网膜中 DA 的早期成熟进行了多次研究，但对年龄较大的大鼠或 OIR 大鼠的研究较少。因此，我们研究了 OIR 大鼠中的 DA、视网膜功能和屈光状态。
在一组大鼠中，使用针对酪氨酸羟化酶（TH，多巴胺生物合成的限速酶）的抗体评估了从 14 至 120 天大鼠的视网膜切片中多巴胺能（DAergic）网络的发育情况。在另一组大鼠中，使用视网膜检影术评估等效球镜（SE），使用视网膜电图（ERG）评估视网膜功能，使用高效液相色谱法（HPLC）评估视网膜中 DA、其前体左旋多巴（DOPA）和主要代谢物 3,4-二羟基苯乙酸（DOPAC）的含量。
正常情况下，DAergic 神经元在出生后迅速分支，但在 OIR 大鼠中这种分支被破坏了。视网膜检影术显示，OIR 大鼠相对近视。在同一只眼睛中，ERG 证实了 OIR 中的视网膜功能障碍。这些眼睛视网膜的 HPLC 分析证实 DA 含量低。回归分析表明，DA 代谢（通过 DOPAC 与 DA 的比值评估）是除 OIR 以外预测近视的重要附加因素。
OIR 大鼠是第一个已知的眼球小于正常大小的近视动物模型。多巴胺可能调节或未能调节 OIR 眼中的神经活动，从而导致这种特殊的近视。
