Abstract

Gamma-amino butyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, including the retina, and play an important role in both regulating neurogenesis and neural stem cell proliferation. GABAa receptor has been identified in the retina, however, the function of GABAa receptor on retinal progenitor cell (RPC) is unclear. RPCs were cultured to analyze changes in cell proliferation and cell cycle distribution after GABAa receptor activation. The activation of GABAa receptor significantly inhibits RPCs proliferation, cell cycle progress, and self-renewal. Moreover, the activation of GABAa receptor leads to the up-expression of p21 and p27 and down-expression of Nestin, Pax6, Sox2, and Chx10. These results suggest that GABA acts as a negative regulator of RPCs proliferation and self-renewal.

Highlights

  • Retinal degeneration diseases, such as retinitis pigmentosa and age-related macular degeneration, which are characterized by photoreceptor degeneration and death, often result in complete vision loss[1]

  • Characterization of primary cultured retinal progenitor cell (RPC) Adult mice retina was digested into single cell and plated on the dish coated with gelatin

  • The present work illustrates that glutamine and γ-amino butyric acid (GABA) signaling could affect proliferation and self-renewal of RPCs

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Summary

Introduction

Retinal degeneration diseases, such as retinitis pigmentosa and age-related macular degeneration, which are characterized by photoreceptor degeneration and death, often result in complete vision loss[1]. Song et al found GABA could directly affect NSCs, and decreased the number and proportion of proliferating NSCs in the dentate gyrus[19] They showed local interneurons could regulate neurogenesis in the distal region through GABA signal pathway[12]. The role of GABA in stem cell regulation is not restricted to the hippocampus, it has been identified as a negative regulator of stem cell proliferation in a number of other contexts, including the embryonic stem cell and spermatogonial stem cells[20,21,22,23] All these results indicated that GABA is an important niche factor to maintain stem cell pool homeostasis in vivo[11,24]

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