Cuenca Nicolás, Pinilla Isabel, Sauvé Yves, Lund Raymond
Moran Eye Center, Ophthalmology and Visual Sciences, 75 North Medical Dr, University of Utah, 84132 Salt Lake City, Utah, USA.
Eur J Neurosci. 2005 Sep;22(5):1057-72. doi: 10.1111/j.1460-9568.2005.04300.x.
The Royal College of Surgeons (RCS) rat has a retinal pigment epithelial cell defect that causes progressive loss of photoreceptors. Although it is extensively used in retinal degeneration and repair studies, how photoreceptor degeneration affects retinal circuitry has not been fully explored. This study examined the changes in synaptic connectivity between photoreceptors and their target cells using immunocytochemistry and correlated these changes with retinal function using the electroretinogram (ERG). Immunostaining with bassoon and synaptophysin (as presynaptic markers) and metabotropic glutamate receptor (mGluR6, a postsynaptic marker for ON-bipolar dendrites) was already impaired at postnatal day (P) 21 and progressively lost with infrequent pairing of presynaptic and postsynaptic elements at P60. By P90 to P120, staining became increasingly patchy and was eventually restricted to sparsely and irregularly distributed foci in which the normal pairing of presynaptic and postsynaptic markers was lost. ERG results showed that mixed scotopic a-waves and b-waves were already reduced by P21 but not oscillatory potentials. While cone-driven responses (photopic b-wave) reached normal levels at P30, they were impaired by P60 but could still be recorded at P120, although with reduced amplitude; rod responses never reached normal amplitudes. Thus, only cone-driven activity attained normal levels, but declined rapidly thereafter. In conclusion, the synaptic markers associated with photoreceptors and processes of bipolar and horizontal cells show abnormalities prior to significant photoreceptor loss. These changes are paralleled with the deterioration of specific aspects of ERG responsiveness with age. Besides providing information on the effects of photoreceptor dysfunction and loss on connection patterns in the retina, the work addresses the more general issue of how disorder of input neurons affects downstream circuitry.
皇家外科学院（RCS）大鼠存在视网膜色素上皮细胞缺陷，可导致光感受器逐渐丧失。尽管它被广泛用于视网膜变性和修复研究，但光感受器变性如何影响视网膜神经回路尚未得到充分探索。本研究使用免疫细胞化学方法检测了光感受器与其靶细胞之间突触连接的变化，并通过视网膜电图（ERG）将这些变化与视网膜功能相关联。在出生后第（P）21天，用巴松管和突触素（作为突触前标记物）以及代谢型谷氨酸受体（mGluR6，ON双极树突的突触后标记物）进行免疫染色就已经受损，并在P60时随着突触前和突触后元件配对减少而逐渐丧失。到P90至P（此处原文有误，推测为P120）时，染色变得越来越斑驳，最终局限于稀疏且不规则分布的病灶，其中突触前和突触后标记物的正常配对丧失。ERG结果显示，混合暗视a波和b波在P21时已经降低，但振荡电位未降低。虽然锥体驱动反应（明视b波）在P30时达到正常水平，但在P60时受损，不过在P120时仍可记录到，尽管振幅降低；杆体反应从未达到正常振幅。因此，只有锥体驱动活动达到正常水平，但此后迅速下降。总之，与光感受器以及双极细胞和水平细胞过程相关的突触标记物在光感受器显著丧失之前就显示出异常。这些变化与ERG反应性随年龄的恶化情况平行。除了提供光感受器功能障碍和丧失对视网膜连接模式影响的信息外，这项工作还解决了输入神经元紊乱如何影响下游神经回路这一更普遍的问题。
