Transgenic Mice Over-Expressing RBP4 Have RBP4-Dependent and Light-Independent Retinal Degeneration.
Transgenic Mice Over-Expressing RBP4 Have RBP4-Dependent and Light-Independent Retinal Degeneration.
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DOI：
10.1167/iovs.17-22107
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发表时间：
2017-08-01
影响因子：
4.4
通讯作者：
Farjo KM
中科院分区：
文献类型：
--
作者：
Du M;Phelps E;Balangue MJ;Dockins A;Moiseyev G;Shin Y;Kane S;Otalora L;Ma JX;Farjo R;Farjo KM
过表达血清视黄醇结合蛋白（RBP 4-Tg）的转基因小鼠发生进行性视网膜变性，其特征在于小胶质细胞活化，但视网膜变性的确切机制尚不清楚。先前的研究表明RBP 4-Tg小鼠具有正常的眼部类维生素A水平，这表明退化与类维生素A视觉周期或光照无关。本研究通过分别测试暗饲养和药物降低血清RBP 4水平的作用来解决视网膜变性是否是光依赖性和RBP 4依赖性的。将在正常循环光照条件下以正常小鼠食物饲养的RBP 4-Tg小鼠与暴露于补充有降低RBP 4的化合物A1120的食物或黑暗饲养条件的RBP 4-Tg小鼠直接比较。进行定量视网膜组织学分析以评估视网膜变性，并进行视网膜电图（ERG）和视动追踪（OKT）测试以评估视网膜和视觉功能。定量眼部类维生素A和双类维生素A 2 E。黑暗饲养的RBP 4-Tg小鼠有效地降低了眼部双类视色素A2 E水平，但对RBP 4-Tg小鼠的视网膜变性或功能障碍没有显著影响，表明视网膜变性是光非依赖性的。A1120处理降低了与野生型小鼠相似的血清RBP 4水平，并防止了结构性视网膜变性。然而，A1120治疗不能预防RBP 4-Tg小鼠的视网膜功能障碍。此外，与正常食物的RBP 4-Tg小鼠相比，A1120饮食的RBP 4-Tg小鼠具有OKT反应的显著恶化和视锥光感受器的损失。这可能与补充A1120的饮食的小鼠视网膜中视黄酯水平非常显著的降低有关。RBP 4-Tg小鼠中的视网膜变性是RBP 4依赖性的并且不依赖于光。
Transgenic mice overexpressing serum retinol-binding protein (RBP4-Tg) develop progressive retinal degeneration, characterized by microglia activation, yet the precise mechanisms underlying retinal degeneration are unclear. Previous studies showed RBP4-Tg mice have normal ocular retinoid levels, suggesting that degeneration is independent of the retinoid visual cycle or light exposure. The present study addresses whether retinal degeneration is light-dependent and RBP4-dependent by testing the effects of dark-rearing and pharmacological lowering of serum RBP4 levels, respectively. RBP4-Tg mice reared on normal mouse chow in normal cyclic light conditions were directly compared to RBP4-Tg mice exposed to chow supplemented with the RBP4-lowering compound A1120 or dark-rearing conditions. Quantitative retinal histological analysis was conducted to assess retinal degeneration, and electroretinography (ERG) and optokinetic tracking (OKT) tests were performed to assess retinal and visual function. Ocular retinoids and bis-retinoid A2E were quantified. Dark-rearing RBP4-Tg mice effectively reduced ocular bis-retinoid A2E levels, but had no significant effect on retinal degeneration or dysfunction in RBP4-Tg mice, demonstrating that retinal degeneration is light-independent. A1120 treatment lowered serum RBP4 levels similar to wild-type mice, and prevented structural retinal degeneration. However, A1120 treatment did not prevent retinal dysfunction in RBP4-Tg mice. Moreover, RBP4-Tg mice on A1120 diet had significant worsening of OKT response and loss of cone photoreceptors compared to RBP4-Tg mice on normal chow. This may be related to the very significant reduction in retinyl ester levels in the retina of mice on A1120-supplemented diet. Retinal degeneration in RBP4-Tg mice is RBP4-dependent and light-independent.
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视网膜类似（视觉）周期的化学。
影响因子：
62.1
作者：
Kiser, Philip D.;Golczak, Marcin;Palczewski, Krzysztof
通讯作者：
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影响因子：
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5.8
作者：
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