Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Neurosci. 2012 Apr 4;32(14):4821-6. doi: 10.1523/JNEUROSCI.5050-11.2012.
The divergence of retinal ganglion cell (RGC) axons into ipsilateral and contralateral projections at the optic chiasm and the subsequent segregation of retinal inputs into eye-specific domains in their target, the dorsal lateral geniculate nucleus (dLGN), are crucial for binocular vision. In albinism, affected individuals exhibit a lack or reduction of pigmentation in the eye and skin, a concomitant reduced ipsilateral projection, and diverse visual defects. Here we investigate how such altered decussation affects eye-specific retinogeniculate targeting in albino mice using the C57BL/6 Tyr(c-2J/c-2J) strain, in which tyrosinase, necessary for melanogenesis, is mutated. In albino mice, fewer RGCs from the ventrotemporal (VT) retina project ipsilaterally, reflected in a decrease in cells expressing ipsilateral markers. In addition, a population of RGCs from the VT retina projects contralaterally and, within the dLGN, their axons cluster into a patch separated from the contralateral termination area. Furthermore, eye-specific segregation is not complete in the albino dLGN and, upon perturbing postnatal retinal activity with epibatidine, the ipsilateral projection fragments and the aberrant contralateral patch disappears. These results suggest that the defects in afferent targeting and activity-dependent refinement in the albino dLGN arise from RGC misspecification together with potential perturbations of early activity patterns in the albino retina.
视网膜神经节细胞（RGC）轴突在视交叉处向同侧和对侧投射的分歧，以及随后视网膜输入在其靶标背外侧膝状体核（dLGN）中特异性地分隔为眼特异性区域，对于双眼视觉至关重要。在白化病中，受影响的个体表现出眼睛和皮肤缺乏或减少色素沉着，伴随同侧投射减少以及各种视觉缺陷。在这里，我们使用 C57BL/6 Tyr(c-2J/c-2J) 品系（其中酪氨酸酶，黑色素生成所必需的，发生突变）研究了这种改变的交叉如何影响白化小鼠的眼特异性视放射状靶向。在白化小鼠中，来自腹侧（VT）视网膜的较少 RGC 同侧投射，反映在表达同侧标记物的细胞减少。此外，来自 VT 视网膜的一部分 RGC 对侧投射，并且在 dLGN 中，它们的轴突聚集在与对侧终止区分离的斑块中。此外，白化 dLGN 中的眼特异性分隔并不完全，并且在用 epibatidine 扰乱出生后视网膜活性后，同侧投射片段化，异常的对侧斑块消失。这些结果表明，在白化 dLGN 中传入靶向和活性依赖性细化的缺陷源于 RGC 的错误指定，以及白化视网膜中早期活性模式的潜在干扰。
