Dynamic functional and structural remodeling during retinal regeneration in zebrafish.
Dynamic functional and structural remodeling during retinal regeneration in zebrafish.
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DOI：
10.3389/fnmol.2022.1070509
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发表时间：
2022
影响因子：
4.8
通讯作者：
Stenkamp, Deborah L.
中科院分区：
文献类型：
--
作者：
Barrett, Lindsey M.;Mitchell, Diana M.;Meighan, Peter C.;Varnum, Michael D.;Stenkamp, Deborah L.
斑马鱼在受损后再生视网膜，从而恢复视觉功能。在这里，我们通过视网膜电图（ERG）的定性和定量分析视网膜损伤后随着时间的推移，与再生视网膜组织的组织学特征的视网膜功能的恢复进行评估。通过玻璃体内注射10 μM（广泛损伤;破坏所有神经元）或2 μM（选择性损伤;备用光感受器）哇巴因来损伤成年斑马鱼的视网膜。未损伤的对侧视网膜作为对照。使用来自活斑马鱼的ERG记录在选定的时间点分析视网膜回路的功能，并且随后立即处理整个眼睛用于组织学分析。在视网膜再生过程中的波形的定性和定量评估揭示了动态变化，在每个采样时间内的个人水平上是异质的，但仍然遵循共同的波形恢复模式的每条鱼和人口水平的基础上。在再生期早期（损伤后13-30天; DPI），对于两种病变类型，基本上未检测到b波，并且a波的表观振幅、隐式时间和半宽（与对照组相比）未掩蔽增加。在对照记录中，d-波没有明显检测到，但明显的d-波（关闭双极反应）从再生视网膜的几条鱼成为突出的30 DPI和占主导地位的感光后反应（PPR）。超过45 DPI，b波变得可检测，并且表观d波与b波贡献的比率逐渐变化，其中大多数但不是全部的鱼显示b波占主导地位的PPR。在最新时间点（广泛，90 DPI;选择性，80 DPI），可测量b波的记录接近正常波形（隐式时间和半宽），但振幅未恢复至对照水平。记录ERG的视网膜的组织学分析显示，随着再生的进展，PKCa + ON双极末端和小清蛋白+无长突细胞过程在每种损伤类型后的恢复时间内变得更加刻板地定位在INL的深层亚层内，与ERG记录中观察到的PPR变化一致。两者合计，这些数据表明，光感受器关闭双极组件/连接可能在功能上恢复和成熟的光感受器上双极组件相比，在再生过程中，虽然这种恢复发生的时间框架是异质的每鱼的基础上。总的来说，我们的研究表明，在视网膜再生过程中，ON双极功能电路逐渐恢复。
Zebrafish regenerate their retinas following damage, resulting in restoration of visual function. Here we evaluate recovery of retinal function through qualitative and quantitative analysis of the electroretinogram (ERG) over time following retinal damage, in correlation to histological features of regenerated retinal tissue. Retinas of adult zebrafish were lesioned by intravitreal injection of 10 μM (extensive lesion; destroys all neurons) or 2 μM (selective lesion; spares photoreceptors) ouabain. Unlesioned contralateral retinas served as controls. Function of retinal circuitry was analyzed at selected timepoints using ERG recordings from live zebrafish, and whole eyes were processed for histological analyses immediately thereafter. Qualitative and quantitative assessment of waveforms during retinal regeneration revealed dynamic changes that were heterogeneous on an individual level within each sampling time, but still followed common waveform recovery patterns on a per-fish and population-level basis. Early in the regeneration period (13–30 days post injury; DPI), for both lesion types, b-waves were essentially not detected, and unmasked increased apparent amplitudes, implicit times, and half-widths of a-waves (vs. controls). In control recordings, d-waves were not obviously detected, but apparent d-waves (OFF-bipolar responses) from regenerating retinas of several fish became prominent by 30DPI and dominated the post-photoreceptor response (PPR). Beyond 45DPI, b-waves became detectable, and the ratio of apparent d- to b-wave contributions progressively shifted with most, but not all, fish displaying a b-wave dominated PPR. At the latest timepoints (extensive, 90DPI; selective, 80DPI), recordings with measurable b-waves approached a normal waveform (implicit times and half-widths), but amplitudes were not restored to control levels. Histological analyses of the retinas from which ERGs were recorded showed that as regeneration progressed, PKCa + ON-bipolar terminals and parvalbumin + amacrine cell processes became more stereotypically positioned within the deep sublaminae of the INL over recovery time after each lesion type, consistent with the shift in PPR seen in the ERG recordings. Taken together, these data suggest that photoreceptor-OFF-bipolar component/connectivity may functionally recover and mature earlier during regeneration compared to the photoreceptor-ON-bipolar component, though the timeframe in which such recovery happens is heterogeneous on a per-fish basis. Collectively our studies suggest gradual restoration of ON-bipolar functional circuitry during retinal regeneration.
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