A novel in vivo model of focal light emitting diode-induced cone-photoreceptor phototoxicity: neuroprotection afforded by brimonidine, BDNF, PEDF or bFGF.
A novel in vivo model of focal light emitting diode-induced cone-photoreceptor phototoxicity: neuroprotection afforded by brimonidine, BDNF, PEDF or bFGF.
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DOI：
10.1371/journal.pone.0113798
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Vidal-Sanz M
中科院分区：
文献类型：
--
作者：
Ortín-Martínez A;Valiente-Soriano FJ;García-Ayuso D;Alarcón-Martínez L;Jiménez-López M;Bernal-Garro JM;Nieto-López L;Nadal-Nicolás FM;Villegas-Pérez MP;Wheeler LA;Vidal-Sanz M
我们研究了发光二极管（LED）诱导的光毒性（LIP）对锥状光感受器的影响以及溴胺（BMD）、脑源性神经营养因子（BDNF）、色素上皮衍生因子（PEDF）、睫状神经营养因子（CNTF）或碱性成纤维细胞生长因子（bFGF）对锥状光感受器的保护作用。在麻醉、适应黑暗的成年白化大鼠中，将蓝色（400 nm） LED垂直放置于角膜（10秒，200 lux），并使用光谱域光学相干断层扫描（SD-OCT）和/或分析定向截面或整体的视网膜，免疫标记L-和s-视蛋白，并用核染色DAPI反染色。局部BMD（1%）或玻璃体内注射BDNF（5µg）、PEDF（2µg）、CNTF（0.4µg）或bFGF（1µg）对LIP后7天全量的影响。SD-OCT显示颞上视网膜圆形区域损伤，直径从1842.4±84.5µm（24小时）到1407.7±52.8µm（7天）不等。该区域的厚度从183.4±5µm （12 h）逐渐减少到114.6±6µm （7 d）。定向横截面显示视网膜光损伤区域内大量杆状和锥状光感受器丢失。Wholemounts记录了一个圆形区域，其中含有较少数量的L型和s型锥体。在左侧和对侧同侧视网膜对应的圆形区域（分别为1mm或1.3 mm半径）内，LED暴露视网膜的L-或s -锥体总数分别为7118±842或661±125 （n = 7）和14,040±1,860或2,255±193 （n = 7）。BMD、BDNF、PEDF和bFGF对L-或s -锥体有显著的神经保护作用，而CNTF没有。我们得出结论，LIP导致杆状和锥状光感受器丧失，是研究锥状光感受器退化的可靠、可量化的模型。在该模型中，玻璃体内BDNF、PEDF或bFGF或局部BMD均具有显著的锥体神经保护作用。
We have investigated the effects of light-emitting diode (LED)-induced phototoxicity (LIP) on cone-photoreceptors and their protection with brimonidine (BMD), brain-derived neurotrophic factor (BDNF), pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF) or basic fibroblast growth factor (bFGF). In anesthetized, dark adapted, adult albino rats a blue (400 nm) LED was placed perpendicular to the cornea (10 sec, 200 lux) and the effects were investigated using Spectral Domain Optical Coherence Tomography (SD-OCT) and/or analysing the retina in oriented cross-sections or wholemounts immune-labelled for L- and S-opsin and counterstained with the nuclear stain DAPI. The effects of topical BMD (1%) or, intravitreally injected BDNF (5 µg), PEDF (2 µg), CNTF (0.4 µg) or bFGF (1 µg) after LIP were examined on wholemounts at 7 days. SD-OCT showed damage in a circular region of the superotemporal retina, whose diameter varied from 1,842.4±84.5 µm (at 24 hours) to 1,407.7±52.8 µm (at 7 days). This region had a progressive thickness diminution from 183.4±5 µm (at 12 h) to 114.6±6 µm (at 7 d). Oriented cross-sections showed within the light-damaged region of the retina massive loss of rods and cone-photoreceptors. Wholemounts documented a circular region containing lower numbers of L- and S-cones. Within a circular area (1 mm or 1.3 mm radius, respectively) in the left and in its corresponding region of the contralateral-fellow-retina, total L- or S-cones were 7,118±842 or 661±125 for the LED exposed retinas (n = 7) and 14,040±1,860 or 2,255±193 for the fellow retinas (n = 7), respectively. BMD, BDNF, PEDF and bFGF but not CNTF showed significant neuroprotective effects on L- or S-cones. We conclude that LIP results in rod and cone-photoreceptor loss, and is a reliable, quantifiable model to study cone-photoreceptor degeneration. Intravitreal BDNF, PEDF or bFGF, or topical BMD afford significant cone neuroprotection in this model.
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影响因子：
3.4
作者：
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通讯作者：
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影响因子：
3.7
作者：
Berger A;Cavallero S;Dominguez E;Barbe P;Simonutti M;Sahel JA;Sennlaub F;Raoul W;Paques M;Bemelmans AP
通讯作者：
Bemelmans AP