Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse
Loss of Outer Retinal Neurons and Circuitry Alterations in the DBA/2J Mouse
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DOI：
10.1167/iovs.14-14421
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发表时间：
2014-09-01
影响因子：
4.4
通讯作者：
Cuenca, Nicolas
中科院分区：
文献类型：
--
作者：
Fernandez-Sanchez, Laura;de Sevilla Mueller, Luis Perez;Cuenca, Nicolas
目的. DBA/2 J小鼠系出现原发性虹膜萎缩、色素分散和青光眼性年龄相关变化，包括IOP升高、视神经萎缩和视网膜神经节细胞（RGC）死亡。本研究的目的是评估DBA/2 J小鼠的视网膜外层可能的形态学变化伴随着疾病的进展和衰老，基于该小鼠系中a-和b-波以及明视闪烁ERG的减少。垂直切片的DBA/2 J小鼠视网膜进行了评估，在3个月，8个月和16个月的年龄使用感光细胞，水平，双极细胞标记。16月龄C57 BL/6小鼠视网膜用作对照。DBA/2 J小鼠在所有年龄段都有外视网膜变性，最老的视网膜变性最严重。在3月龄时，感光细胞的数量和OPL的厚度减少。此外，有一个损失的水平和ON双极细胞的过程。在8个月的年龄，RGC变性发生在补丁，并在外层视网膜覆盖这些补丁，锥形态受损的大小减少，以及损失的外段和增长的水平和双极细胞进程到外核层。在16个月大时，光感受器与覆盖这些斑块的水平和双极细胞突起之间的连接丢失。DBA/2 J小鼠的视网膜变性包括感光细胞死亡、双极和水平细胞突起的丧失以及以衰老依赖性方式的突触接触的丧失。
PURPOSE. The DBA/2J mouse line develops essential iris atrophy, pigment dispersion, and glaucomatous age-related changes, including an increase of IOP, optic nerve atrophy, and retinal ganglion cell (RGC) death. The aim of this study was to evaluate possible morphological changes in the outer retina of the DBA/2J mouse concomitant with disease progression and aging, based on the reduction of both the a-and b-waves and photopic flicker ERGs in this mouse line.METHODS. Vertically sectioned DBA/2J mice retinas were evaluated at 3, 8, and 16 months of age using photoreceptor, horizontal, and bipolar cell markers. Sixteen-month-old C57BL/6 mice retinas were used as controls.RESULTS. The DBA/2J mice had outer retinal degeneration at all ages, with the most severe degeneration in the oldest retinas. At 3 months of age, the number of photoreceptor cells and the thickness of the OPL were reduced. In addition, there was a loss of horizontal and ONbipolar cell processes. At 8 months of age, RGC degeneration occurred in patches, and in the outer retina overlying these patches, cone morphology was impaired with a reduction in size as well as loss of outer segments and growth of horizontal and bipolar cell processes into the outer nuclear layer. At 16 months of age, connectivity between photoreceptors and horizontal and bipolar cell processes overlying these patches was lost.CONCLUSIONS. Retinal degeneration in DBA/2J mice includes photoreceptor death, loss of bipolar and horizontal cell processes, and loss of synaptic contacts in an aging-dependent manner.