Semo Ma'ayan, Coffey Peter, Gias Carlos, Vugler Anthony
Department of Ocular Biology and Therapeutics UCL-Institute of Ophthalmology, London, United Kingdom.
Department of Ocular Biology and Therapeutics UCL-Institute of Ophthalmology, London, United Kingdom 2Neuroscience Research Institute, University of California-Santa Barbara, Santa Barbara, California, United States.
Invest Ophthalmol Vis Sci. 2016 Jan 1;57(1):115-25. doi: 10.1167/iovs.15-17609.
Following on from reports of retrograde retinal signaling in mice, we sought to investigate the influence of age and retinal location on this phenomenon using mice that lack rods and the majority of cones.
We used functional anatomy for c-fos (Fos) and tyrosine hydroxylase (TH) to measure light-driven activation of dopamine neurons along a dorsal-ventral transect in C3H/He wild-type and rodless-coneless rd/rd cl (rdcl) mice aged 3, 5, and >14 months. A parallel series of retinae from 3-month-old mice was also stained for cone opsins and melanopsin.
Analysis by confocal microscopy revealed light-driven Fos activation in TH cells residing in the middorsal retina of the youngest rdcl mice. This region was largely devoid of residual cones but contained a large number of intrinsically photosensitive retinal ganglion cells (ipRGCs) and the highest density of melanopsin neurites. With advancing age, there was a paradoxical increase in retrograde signaling from ∼3% Fos-positive (Fos+) TH cells at 3 months to ∼36% in rdcl mice >14 months. This increased activation occurred in more central and peripheral retinal regions.
Our data provide new insights into the anatomy and plasticity of retrograde melanopsin signaling in mice with severe rod/cone dystrophy. The increased retrograde signaling we detect may result from either an increased potency of melanopsin signaling with advancing age and/or postsynaptic modification to dopaminergic neurons.
继小鼠逆行视网膜信号传导的报道之后，我们试图使用缺乏视杆细胞和大部分视锥细胞的小鼠，研究年龄和视网膜位置对这一现象的影响。
我们利用c-fos（Fos）和酪氨酸羟化酶（TH）的功能解剖学方法，测量3、5和大于14月龄的C3H/He野生型以及无杆无锥的rd/rd cl（rdcl）小鼠沿背腹横断面的多巴胺能神经元的光驱动激活情况。还对3月龄小鼠的平行系列视网膜进行了视锥视蛋白和黑视蛋白染色。
共聚焦显微镜分析显示，在最年幼的rdcl小鼠中，位于视网膜中背侧的TH细胞存在光驱动的Fos激活。该区域基本没有残留视锥细胞，但含有大量内在光敏性视网膜神经节细胞（ipRGCs）以及最高密度的黑视蛋白神经突。随着年龄增长，逆行信号传导出现矛盾性增加，从3月龄时约3%的Fos阳性（Fos+）TH细胞增加到大于14月龄的rdcl小鼠中的约36%。这种激活增加发生在视网膜更中央和周边区域。
我们的数据为严重视杆/视锥营养不良小鼠中逆行黑视蛋白信号传导的解剖学和可塑性提供了新见解。我们检测到的逆行信号传导增加可能是由于随着年龄增长黑视蛋白信号传导效力增加和/或多巴胺能神经元的突触后修饰所致。
