Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin.
Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin.
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DOI：
10.1084/jem.20041447
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发表时间：
2004-12-20
期刊：
影响因子：
--
通讯作者：
Finnemann SC
中科院分区：
文献类型：
--
作者：
Nandrot EF;Kim Y;Brodie SE;Huang X;Sheppard D;Finnemann SC
消费光感受器外部段片段的视网膜色素上皮（RPE）每日吞噬作用对于视网膜中的视力至关重要。受体αVβ5用于粒子结合，我们在β5整合素缺乏的小鼠中测试了RPE吞噬作用和残留功能αVβ5受体在β5 - / - 小鼠中的年龄严重下降，其RPE积累了自动荧光储存体，这是人类残留衰老和疾病的标志。 - RPE在体内保留了基本吸收水平，但缺乏昼夜型光感受器在野生型RPE中脱落后的吞噬活性。在β5 - / - 视网膜中，介导野生型视网膜吞噬作用的粘附和MER酪氨酸激酶也完全不存在。 / - 整合素小鼠菌株作为与年龄相关的视网膜功能障碍的新动物模型。
Daily phagocytosis by the retinal pigment epithelium (RPE) of spent photoreceptor outer segment fragments is critical for vision. In the retina, early morning circadian photoreceptor rod shedding precedes synchronized uptake of shed photoreceptor particles by RPE cells. In vitro, RPE cells use the integrin receptor αvβ5 for particle binding. Here, we tested RPE phagocytosis and retinal function in β5 integrin–deficient mice, which specifically lack αvβ5 receptors. Retinal photoresponses severely declined with age in β5−/− mice, whose RPE accumulated autofluorescent storage bodies that are hallmarks of human retinal aging and disease. β5−/− RPE in culture failed to take up isolated photoreceptor particles. β5−/− RPE in vivo retained basal uptake levels but lacked the burst of phagocytic activity that followed circadian photoreceptor shedding in wild-type RPE. Rhythmic activation of focal adhesion and Mer tyrosine kinases that mediate wild-type retinal phagocytosis was also completely absent in β5−/− retina. These results demonstrate an essential role for αvβ5 integrin receptors and their downstream signaling pathways in synchronizing retinal phagocytosis. Furthermore, they identify the β5−/− integrin mouse strain as a new animal model of age-related retinal dysfunction.
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DOI：
10.1083/jcb.49.2.303
发表时间：
1971-05-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Young RW
通讯作者：
Young RW
DOI：
10.1084/jem.194.9.1289
发表时间：
2001-11-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Finnemann SC;Silverstein RL
通讯作者：
Silverstein RL
影响因子：
6.1
作者：
Nandrot, E;Dufour, EM;Abitbol, MM
通讯作者：
Abitbol, MM
影响因子：
56.9
作者：
LAVAIL, MM
通讯作者：
LAVAIL, MM
影响因子：
5.3
作者：
Huang, XZ;Griffiths, M;Sheppard, D
通讯作者：
Sheppard, D