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Cell survival controlled by lens-derived Sema3A-Nrp1 is vital on caffeine-suppressed corneal innervation during chick

Guang Wang1,2, Ling-Min Jiang1, Bao-Yi Tan1

  • 1Department of Histology and Embryology, International Joint Laboratory for Embryonic Development & Prenatal Medicine, Medical College, Jinan University, Guangzhou, China.

Journal of Cellular Physiology
|October 27, 2018
PubMed

Insights

Caffeine overexposure in chicken embryos impairs corneal nerve development by affecting trigeminal nerve growth. This study reveals caffeine-induced reactive oxygen species upregulate Sema3A-Nrp1 signaling, leading to corneal cell apoptosis.

Area of Science:

  • Developmental biology
  • Neuroscience
  • Ophthalmology

Background:

  • Corneal innervation is crucial for ocular surface health and function.
  • Understanding factors affecting early nerve development is vital for preventing congenital eye disorders.

Purpose of the Study:

  • To investigate the impact of caffeine overexposure on corneal innervation in early chicken embryos.
  • To elucidate the molecular mechanisms underlying caffeine's effects on trigeminal nerve development and corneal cell survival.

Main Methods:

  • Immunohistochemistry for cell proliferation (phospho-Histone3) and apoptosis (C-caspase3).
  • Whole-mount in situ hybridization for semaphorin 3A (Sema3A) and neuropilin-1 (Nrp1) expression.
  • Lens ablation experiments and in vitro neuroblastoma cell line studies.

Main Results:

  • Caffeine administration restricted corneal innervation and repressed cell survival.
  • Caffeine and free radical generator (AAPH) upregulated Sema3A and Nrp1 expression.
  • Sema3A knockdown reduced caffeine's effects on cell apoptosis and responsiveness.

Conclusions:

  • Caffeine-enhanced reactive oxygen species may upregulate Sema3A-Nrp1 signaling, causing corneal cell apoptosis.
  • Sema3A-Nrp1 signaling appears to regulate Trp53 and Cdkn1a, influencing trigeminal nerve invasion of the cornea.
Keywords:
Sema3A-Nrp1 signalingcaffeinecell survivalchicken embryocorneal innervation

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