APOMORPHINE BLOCKS FORM-DEPRIVATION MYOPIA IN CHICKENS BY A DOPAMINE D2-RECEPTOR MECHANISM ACTING IN RETINA OR PIGMENTED EPITHELIUM
APOMORPHINE BLOCKS FORM-DEPRIVATION MYOPIA IN CHICKENS BY A DOPAMINE D2-RECEPTOR MECHANISM ACTING IN RETINA OR PIGMENTED EPITHELIUM
复制标题
DOI：
10.1017/s0952523800004673
复制
发表时间：
1993-05-01
影响因子：
1.9
通讯作者：
STELL, WK
中科院分区：
文献类型：
--
作者：
ROHRER, B;SPIRA, AW;STELL, WK
在动物模型中进行的形觉剥夺性近视（FDM）的研究表明，出生后眼球的生长受到视网膜上图案图像质量的调节。近视研究的主要挑战之一是确定将视网膜视觉反应转化为调节巩膜生长的信号的生化机制。多巴胺（DA）与该过程有关，因为FDM中视网膜DA水平下降，并且结膜下注射阿朴吗啡（Apo，一种非特异性DA激动剂）以剂量依赖性方式预防FDM（Stone et al.，为了深入了解DA配体在何处以及如何调节眼伸长，我们比较了在幼鸡中玻璃体内注射与结膜下注射的DA受体配体的作用和分布。A超测量眼球长度。我们发现，每天玻璃体内注射Apo以50%有效剂量（ED 50）5 μ g/天阻断FDM，或玻璃体液中的峰值浓度为108 pM，而Stone等人（1989，1990）报道的结膜下注射的ED 50为2.5 ng。[H-3]-螺哌隆是一种D2受体拮抗剂，在ED 50剂量下，在玻璃体内和结膜下给药后的第一个小时内，其平均最大视网膜浓度分别达到160 pM和260 pM。相比之下，玻璃体内或结膜下ED 50给药后，视网膜色素上皮（RPE）中的最大螺哌隆浓度分别为30 pM和410 pM。两个部位ED 50给药后巩膜中的螺哌隆浓度相差4 x 10（4）（分别为0.4 pM和1.7 nM）。Apo的FDM预防作用被同时给予螺哌隆完全阻断，但不被SCH 23390（一种D1受体拮抗剂）以100倍摩尔过量阻断。这些结果表明，无论是玻璃体内给药还是结膜下给药，阿扑吗啡都能在眼内部位预防FDM，推测是在视网膜和/或色素上皮，而不是巩膜。产生100-260 pM浓度的剂量，每天小于或等于1小时递送，产生半数最大抑制。该作用由D2受体介导，其对阿扑吗啡的解离常数小于或等于1 nM。视网膜色素上皮细胞可能作为营养中继站，响应视网膜信使（可能是DA）并从其基底表面分泌巩膜生长调节剂。
Studies of form-deprivation myopia (FDM) in animal models have shown that postnatal ocular growth is regulated by the quality of patterned images on the retina. One of the major challenges in myopia research is to identify the biochemical mechanisms which translate retinal visual responses into signals that regulate scleral growth. Dopamine (DA) has been implicated in this process, since retinal DA levels decline in FDM and subconjunctival injections of apomorphine (Apo, a nonspecific DA agonist) prevent FDM in a dose-dependent way (Stone et al., 1989).To gain insight into where and how DA ligands act to regulate ocular elongation, we compared the action and distribution of DA receptor ligands injected intravitreally vs. subconjunctivally in young chicks. Ocular length was measured by A-scan ultrasound. We found that daily intravitreal injections of Apo block FDM at a 50% effective dose (ED50) of 5 pg per day, or a peak concentration in the vitreous humor of 108 pM, compared to an ED50 of 2.5 ng for subconjunctival injections as reported by Stone et al. (1989, 1990). [H-3]-spiperone, a D2-receptor antagonist, reached average maximum retinal concentrations of 160 pM and 260 pM, during the first hour after intravitreal and subconjunctival administration, respectively, at the ED50 dose. In contrast, the maximum spiperone concentrations in the retinal pigment epithelium (RPE) were 30 pM and 410 pM, respectively, after intravitreal or subconjunctival ED50 doses. Spiperone concentrations in sclera after ED50 doses to the two sites differed by 4 x 10(4) (0.4 pM vs. 1.7 nM, respectively). The FDM-preventing action of Apo was blocked completely by simultaneous administration of spiperone but not by SCH 23390 (a D1-receptor antagonist) in 100-fold molar excess.These results show that apomorphine acts to prevent FDM at an intraocular site, presumably in retina and/or pigment epithelium, but not sclera, whether administered intravitreally or subconjunctivally. A dose yielding a concentration of 100-260 pM, delivered less-than-or-equal-to 1 h per day, produces half-maximal inhibition. This action is mediated by D2-receptors, for which the dissociation constant for apomorphine is less-than-or-equal-to 1 nM. The retinal pigment epithelium may act as a trophic relay station, responding to a retinal messenger which may be DA and secreting scleral growth-regulator(s) from its basal surface.