Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse
Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse
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DOI：
10.1073/pnas.95.14.8357
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发表时间：
1998-07-07
影响因子：
11.1
通讯作者：
Sahel, JA
中科院分区：
文献类型：
--
作者：
Mohand-Said, S;Deudon-Combe, A;Sahel, JA
研究了遗传性视网膜变性中细胞相互作用在继发性视锥光感受器变性机制中的作用，其中突变特异性地影响视杆光感受器。我们开发了一个器官培养模型的整个视网膜从5周龄小鼠携带视网膜变性突变，其中在这个年龄含有少量剩余的杆和许多幸存的锥共培养的混合细胞的原代培养物从出生后第8天正常视力的小鼠（C57 BL/6）视网膜或视网膜外植体从正常（C57 BL/6）或营养不良（C3 H/He）Ei周龄的小鼠。7天后，通过使用无偏体视学方法在特异性花生凝集素或抗抑制蛋白抗体标记后定量残留视锥光感受器的数量。对器官培养的视网膜的检查显示，与对照组或与剥夺视杆细胞的视网膜共培养物相比，如果在含有正常视杆细胞的视网膜存在下培养，则存活视锥细胞的数量显著更大（15-20%）。这些数据表明存在一种从含有视杆细胞的视网膜释放的可扩散的营养因子，并作用于仅存在视锥细胞的视网膜。由于视锥细胞负责高敏锐度和色觉，因此这些数据不仅对人类视网膜变性的最终治疗方法，而且对定义视网膜感光细胞类型之间的相互作用具有重要意义。
The role of cellular interactions in the mechanism of secondary cone photoreceptor degeneration in inherited retinal degenerations in which the mutation specifically affects rod photoreceptors was studied. We developed an organ culture model of whole retinas from 5-week-old mice carrying the retinal degeneration mutation, which at this age contain few remaining rods and numerous surviving cones cocultured with primary cultures of mixed cells from postnatal day 8 normal-sighted mice (C57BL/6) retinas or retinal explants from normal (C57BL/6) or dystrophic (C3H/He) Ei-week-old mice. After 7 days, the numbers of residual cone photoreceptors were quantified after specific peanut lectin or anti-arrestin antibody labeling by using an unbiased stereological approach. Examination of organ cultured retinas revealed significantly greater numbers of surviving cones (15-20%) if cultured in the presence of retinas containing normal rods as compared with controls or cocultures with rod-deprived retinas. These data indicate the existence of a diffusible trophic factor released from retinas containing rod cells and acting on retinas in which only cones are present. Because cones are responsible for high acuity and color vision, such data could have important implications not only for eventual therapeutic approaches to human retinal degenerations but also to define interactions between retinal photoreceptor types.