Müller cells derived neurotrophin-3 inhibits hypoxia-induced photoreceptor apoptosis via the TrkC/ERK pathway

  • Na Li
  • Yanji Zhu
  • Jing Wang
  • Minqi Zhu
  • Shuang Gao
  • Qi Chen
  • Xi ShenEmail author
Original Article


Neurotrophin-3 (NT-3), a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC) receptor, has been shown to play a crucial role in proliferation, differentiation, and survival. However, the role of NT-3 in the hypoxia-induced retinopathy has not been investigated extensively. Here, we created a model of hypoxia (1% O2) in vitro and found that hypoxia promoted the apoptosis of mouse cone photoreceptor-derived 661W cells, increased the expression of TrkC and cleaved caspase-3. In contrast, the hypoxia-mediated 661W cell apoptosis was markedly alleviated by co-culturing with primary mouse Müller cells. Further mechanism studies revealed that hypoxia increased the synthesis and secretion of NT-3 by Müller cells, and exogenous NT-3 stimulation increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 by binding to TrkC in 661W cells. Besides, both siRNA knockdown of TrkC expression and incubation with an ERK-specific inhibitor PD98059 triggered apoptosis in hypoxic 661W cells. Altogether, these data suggest that NT-3 originating from Müller cells protects photoreceptors from hypoxia-induced apoptosis through a TrkC/ERK-dependent pathway. Our findings may facilitate future studies on the therapeutic implications of NT-3 in the treatment of hypoxia-relevant retinal diseases.


Neurotrophin-3 Photoreceptor apoptosis Tyrosine kinase C Müller cells Hypoxia 



This study was supported by Grants from National Natural Science Foundation of China (Nos. 81670861, 81800826).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to report.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Ophthalmology, Ruijin HospitalAffiliated Shanghai Jiaotong University School of MedicineShanghaiChina

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