L-Dopa and the albino riddle: content of L-Dopa in the developing retina of pigmented and albino mice.
L-Dopa and the albino riddle: content of L-Dopa in the developing retina of pigmented and albino mice.
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DOI：
10.1371/journal.pone.0057184
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mason CA
中科院分区：
文献类型：
--
作者：
Roffler-Tarlov S;Liu JH;Naumova EN;Bernal-Ayala MM;Mason CA
白化病患者缺乏或缺乏黑色素，会对视网膜发育产生不利影响，包括从眼睛到大脑的轴突投射异常和视力受损。在色素性视网膜色素上皮 (RPE) 中，二羟基苯丙氨酸 (L-Dopa) 是黑色素合成途径的中间体，据推测可以调节神经发生的速度。视网膜左旋多巴表达的时间过程、是否仅存在于 RPE 中、白化病患者与同基因对照相比的缺陷程度，以及如果外源递送至白化病患者左旋多巴是否可以恢复，这些尚不清楚。 L-多巴和儿茶酚胺，包括从色素 (C57BL/6J) 和同源白化小鼠 (C57BL/6J-tyrc2j) 小鼠视网膜中提取的多巴胺，在从 E10.5 开始到成熟的整个发育过程中进行测量。一旦酪氨酸酶在 E10.5 的 RPE 中表达，左旋多巴（而不是多巴胺或任何其他儿茶酚胺）就会出现在色素视网膜中。在色素视网膜中，左旋多巴含量在产前和产后发育过程中不断增加，直到产后第一个月末，随后急剧下降。这个时间过程反映了视网膜发育的开始和完成。胚胎白化视网膜中不存在左旋多巴，与色素性视网膜相比，出生后白化视网膜中的左旋多巴大大减少。在神经元酶酪氨酸羟化酶出生后表达之前，白化视网膜和色素视网膜中都检测不到多巴胺。如果向怀孕的白化病母亲提供左旋多巴，左旋多巴会积聚在胎儿的视网膜色素上皮中。着色 RPE 中的左旋多巴在发育过程中最为丰富，此后含量下降。这种左旋多巴不会转化为多巴胺。白化视网膜中左旋多巴不存在或水平较低，可通过子宫内给药将其恢复至 RPE。这些发现进一步表明左旋多巴是 RPE 中可能影响发育的一个因素，并证明左旋多巴的给药可能是挽救白化病患者发育异常特征的一种手段。
The absence or deficiency of melanin as in albinos, has detrimental effects on retinal development that include aberrant axonal projections from eye to brain and impaired vision. In pigmented retinal pigment epithelium (RPE), dihydroxyphenalanine (L-Dopa), an intermediate in the synthetic path for melanin, has been hypothesized to regulate the tempo of neurogenesis. The time course of expression of retinal L-Dopa, whether it is harbored exclusively in the RPE, the extent of deficiency in albinos compared to isogenic controls, and whether L-Dopa can be restored if exogenously delivered to the albino have been unknown. L-Dopa and catecholamines including dopamine extracted from retinas of pigmented (C57BL/6J) and congenic albino (C57BL/6J-tyrc2j) mice, were measured throughout development beginning at E10.5 and at maturity. L-Dopa, but not dopamine nor any other catecholamine, appears in pigmented retina as soon as tyrosinase is expressed in RPE at E10.5. In pigmented retina, L-Dopa content increases throughout pre- and postnatal development until the end of the first postnatal month after which it declines sharply. This time course reflects the onset and completion of retinal development. L-Dopa is absent from embryonic albino retina and is greatly reduced in postnatal albino retina compared to pigmented retina. Dopamine is undetectable in both albino and pigmented retinas until after the postnatal expression of the neuronal enzyme tyrosine hydroxylase. If provided to pregnant albino mothers, L-Dopa accumulates in the RPE of the fetuses. L-Dopa in pigmented RPE is most abundant during development after which content declines. This L-Dopa is not converted to dopamine. L-Dopa is absent or at low levels in albino retina and can be restored to the RPE by administration in utero. These findings further implicate L-Dopa as a factor in the RPE that could influence development, and demonstrate that administration of L-Dopa could be a means to rescue developmental abnormalities characteristic of albinos.
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DOI：
10.3109/13816819009020977
发表时间：
1990-09-01
期刊：
OPHTHALMIC PAEDIATRICS AND GENETICS
影响因子：
--
作者：
GUILLERY, RW
通讯作者：
GUILLERY, RW
DOI：
10.1002/neu.20200
发表时间：
2006-01-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Kraij-Hans, I;Tibber, M;Mobbs, P
通讯作者：
Mobbs, P
DOI：
10.3109/13816819009020979
发表时间：
1990-09-01
期刊：
OPHTHALMIC PAEDIATRICS AND GENETICS
影响因子：
--
作者：
CREEL, DJ;SUMMERS, CG;KING, RA
通讯作者：
KING, RA
DOI：
10.1111/j.1600-0749.2004.00158.x
发表时间：
2004-08-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Giménez, E;Lavado, A;Montoliu, L
通讯作者：
Montoliu, L
影响因子：
4.8
作者：
Eisenhofer, G;Tian, H;Hearing, VJ
通讯作者：
Hearing, VJ