Abstract
Purpose :
GABA receptors (GABAr)are inhibitory receptors activated by GABA, playing a crucial role in neuronal communication with a typical cell hyperpolarization response. However, in glial cells, GABAr involvement extends to homeostatic processes, such as proliferation and cell migration. Interestingly, the physiological function of GABAr in Müller glial cells remains poor explored. Besides, several retinopathies present reactive gliosis from Müller cells accelerating the degenerative neuronal degeneration. This study aimed to investigate the effect of GABAr activation on Müller glial cell gliotic proliferation.
Methods :
Primary Müller glial cell cultures obtained from CD1 mice were exposed to GABA and their agonist for 48 hours. GABA-induced cell proliferation was evaluated by the number of nuclei, trypan blue cell exclusion, and BrdU incorporation into newly divided cells. Additionally, cells were exposed to GABA receptor agonists and antagonists (muscimol, baclofen, gabazine, or CGP55845, respectively) to determine the pharmacological sensitivity of the proliferative process observed with GABA. Furthermore, an extracellular calcium-free medium, nimodipine, and FR-180204 were used to assess the involvement of extracellular calcium and MAPK (ERK1/2) signaling pathway in this mechanism.
Results :
Results indicate that GABA induces a dose-dependent increase in cell number. Moreover, this cellular increase is mimicked by muscimol and blocked with gabazine, an agonist and antagonist of GABAAR respectively. Baclofen, a GABAB receptor agonist, failed to stimulate the proliferation in the Müller glial cells. Finally, the absence of extracellular calcium, as well as blocking L-type calcium channels (LTCC) with nimodipine or inhibiting ERK1/2 proteins phosphorylation, prevented the increase in Müller glial cell proliferation.
Conclusions :
The presented results suggest that GABA induces cell proliferation in Müller glial cells, possibly through the GABA/GABAAR/LTCC/ERK1/2 signaling pathway.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.