Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn3a
Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive Retinal Ganglion Cells and Increases Their Coexpression of Brn3a
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DOI：
10.1167/iovs.15-16808
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发表时间：
2015-07-01
影响因子：
4.4
通讯作者：
Villegas-Perez, Maria P.
中科院分区：
文献类型：
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作者：
Garcia-Ayuso, Diego;Di Pierdomenico, Johnny;Villegas-Perez, Maria P.
目的.目的研究遗传性光感受器变性大鼠模型P23 H-1中视网膜内光敏神经节细胞（melanopsin-expressing RGCs，m（+）RGCs）的数量。在出生后（P）时间P30、P365和P540，将来自P23 H营养不良大鼠（系1，快速变性;和系3，缓慢变性）和Sprague道利（SD）大鼠（对照）的视网膜作为整体切片（whole-mount）进行解剖，并免疫检测黑视蛋白和/或Brn 3 a。定量m（+）RGCs的树突状分支以及Brn 3a（+）RGCs和m（+）RGCs的数量，并分析它们的视网膜分布和共表达。在SD大鼠中，衰老不影响Brn 3a（+）RGCs或m（+）RGCs的数量或显示共表达的百分比（0.27%）。年轻的P23 H-1大鼠Brn 3a（+）RGCs数量显著减少，并随年龄增长而进一步下降。幼年P23 H-1大鼠的m（+）RGCs数量与SD大鼠相似，在P365和P540分别减少22.6%和28.2%，与Brn 3a（+）RGCs的减少相似。在这些年龄段，m（+）RGCs显示其树突状分支参数减少，这在P23 H-1和P23 H-3系中相似。然而，Brn 3a的共表达百分比在P30时已经显着较高（3.31%），并随着年龄的增长显着增加（P540时为10.65%）。结论。遗传性光感受器变性之后是Brn 3a（+）RGC和m（+）RGC的继发性损失。存活的m（+）RGC显示树突状分支参数降低，Brn 3a和黑视素共表达增加，表型和分子变化可能代表能够合成Brn 3a的m（+）RGC抵抗变性和/或优先存活的努力。
PURPOSE. To study the population of intrinsically photosensitive retinal ganglion cells (melanopsin-expressing RGCs, m(+)RGCs) in P23H-1 rats, a rat model of inherited photoreceptor degeneration.METHODS. At postnatal (P) times P30, P365, and P540, retinas from P23H dystrophic rats (line 1, rapid degeneration; and line 3, slow degeneration) and Sprague Dawley (SD) rats (control) were dissected as whole-mounts and immunodetected for melanopsin and/or Brn3a. The dendritic arborization of m(+)RGCs and the numbers of Brn3a(+)RGCs and m(+)RGCs were quantified and their retinal distribution and coexpression analyzed.RESULTS. In SD rats, aging did not affect the population of Brn3a(+)RGCs or m(+)RGCs or the percentage that showed coexpression (0.27%). Young P23H-1 rats had a significantly lower number of Brn3a(+)RGCs and showed a further decline with age. The population of m(+)RGCs in young P23H-1 rats was similar to that found in SD rats and decreased by 22.6% and 28.2% at P365 and P540, respectively, similarly to the decrease of the Brn3a(+)RGCs. At these ages the m(+)RGCs showed a decrease of their dendritic arborization parameters, which was similar in both the P23H-1 and P23H-3 lines. The percentage of coexpression of Brn3a was, however, already significantly higher at P30 (3.31%) and increased significantly with age (10.65% at P540).CONCLUSIONS. Inherited photoreceptor degeneration was followed by secondary loss of Brn3a(+)RGCs and m(+)RGCs. Surviving m(+)RGCs showed decreased dendritic arborization parameters and increased coexpression of Brn3a and melanopsin, phenotypic and molecular changes that may represent an effort to resist degeneration and/or preferential survival of m(+)RGCs capable of synthesizing Brn3a.