Rohrer B, Iuvone P M, Stell W K
University of Calgary, Department of Anatomy, AB, Canada.
Brain Res. 1995 Jul 24;686(2):169-81. doi: 10.1016/0006-8993(95)00370-6.
Form-deprivation myopia (FDM) in the chick is a popular model for studying the postnatal regulation of ocular growth. Using this model, we have shown previously that dopamine and FGF-2 can counteract the effects of form-deprivation, thereby producing emmetropia. In the present study, we tested the hypothesis that the emmetropizing effects of flickering light and intraocular injections of FGF-2 in the chick are mediated by the activity of dopaminergic retinal amacrine cells. We have assessed the rate of dopamine synthesis in the retina by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA). We found that form-deprivation reduces the rate of dopamine synthesis in the light-adapted retina, and that the normal rate of dopamine synthesis in the light can be restored by stroboscopic illumination at frequencies around 10 Hz. By labeling cells immunocytochemically we have shown that the synthesis of c-fos, a putative transcriptional regulator of the tyrosine hydroxylase gene, is induced in dopaminergic amacrine cells by stroboscopic illumination at around 10 Hz. These observations are consistent with a critical role for dopaminergic amacrine cells in the regulation of ocular growth by intermittent illumination. We have found also that intraocular injections of FGF-2 cause emmetropization without altering levels of expression of c-fos, amounts of tyrosine hydroxylase, or rates of dopamine synthesis with respect to vehicle-injected controls. We conclude that FGF acts either in parallel to or downstream from the dopaminergic amacrine cells, rather than through them. We observed that intravitreal injection per se induces high levels of c-fos expression in both form-deprived and non-deprived retinas, and causes partial emmetropization in form-deprived eyes, while inhibiting dopamine synthesis in non-deprived retinas. It is likely, therefore, that injection stimulates the production and/or release of unknown factors whose diverse effects on ocular growth and dopamine metabolism are mediated by complex pathways. Taken together, our results are consistent with the view that the retinal circuitry that controls postnatal ocular growth in the chick involves multiple messengers and pathways.
雏鸡的形觉剥夺性近视（FDM）是研究出生后眼球生长调节的常用模型。利用该模型，我们之前已表明多巴胺和FGF-2可抵消形觉剥夺的影响，从而产生正视化。在本研究中，我们检验了以下假设：雏鸡中闪烁光和眼内注射FGF-2的正视化作用是由多巴胺能视网膜无长突细胞的活性介导的。我们通过测量3,4-二羟基苯丙氨酸（DOPA）的积累来评估视网膜中多巴胺的合成速率。我们发现形觉剥夺会降低光适应视网膜中多巴胺的合成速率，而通过10 Hz左右频率的频闪照明可恢复光下正常的多巴胺合成速率。通过免疫细胞化学标记细胞，我们已表明，在10 Hz左右的频闪照明下，多巴胺能无长突细胞中可诱导c-fos的合成，c-fos是酪氨酸羟化酶基因的一种假定转录调节因子。这些观察结果与多巴胺能无长突细胞在间歇性照明调节眼球生长中起关键作用一致。我们还发现，眼内注射FGF-2可导致正视化，而相对于注射赋形剂的对照组，c-fos的表达水平、酪氨酸羟化酶的量或多巴胺的合成速率均未改变。我们得出结论，FGF的作用要么与多巴胺能无长突细胞平行，要么在其下游，而非通过它们起作用。我们观察到，玻璃体内注射本身会在形觉剥夺和未形觉剥夺的视网膜中均诱导高水平的c-fos表达，并在形觉剥夺的眼中导致部分正视化，同时抑制未形觉剥夺视网膜中的多巴胺合成。因此，注射可能刺激了未知因子的产生和/或释放，这些因子对眼球生长和多巴胺代谢的不同影响是由复杂途径介导的。综上所述，我们的结果与以下观点一致：控制雏鸡出生后眼球生长的视网膜回路涉及多种信使和途径。
