Glucagon as a novel neuromodulator of retinal rod bipolar cell inhibitory activity, possible implications in myopia pathogenesis
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2022-09
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Universidad de Valparaíso
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Facultad de Ciencias
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Programa de Doctorado en Ciencias con mencion en Neurociencias
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Doctor en Ciencias mención en Neurociencia
Resumen
Myopia incidence is steadily increasing worldwide, but the underlying pathophysiologic mechanisms are still only partially understood. Glucagon is a peptide thought to signal image defocus in the eye, which is considered the first step in myopia induction, and dopamine is known for its key role in myopia, being proposed as the main signaling molecule linked to its pathogenesis. The aim of this study was to corroborate glucagon signaling in the mammalian retina and find a possible link with dopaminergic signaling. To this end, whole-cell patch-clamp and bath application of selective pharmacological agents were used to study the inhibitory activity of rod bipolar cells (RBCs), as this activity is known to be regulated by dopamine and has been linked in other parts of the central nervous system to regulation by members of the glucagon/secretin family, and also since RBCs have been implicated in glucagon-related activity. Inhibitory post-synaptic currents (IPSCs) under 0 mV voltage-clamp mode were measured in RBCs from wild-type and lens-induced myopia model mice. Glucagon produced a dose-dependent and glucagon receptor-dependent increase in RBC glycinergic IPSC frequency. This effect was also dependent on dopaminergic activity as it was abolished by dopamine type 1 receptor (D1R) antagonism and in scotopic conditions. The effect was also abolished in the myopia murine model but could be recovered using D1R agonism in model animals for up to 2 weeks of induction. Glucagon is a novel retinal neuromodulator in mammals, regulating the glycinergic inhibitory activity acting on RBCs in a D1R-dependent manner. Its effects are abolished in a myopia model, suggesting it is one of the pathways affected in this condition. More research will be required to determine whether this pathway could be a target for myopia prevention or treatment.
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MIOPIA, GLUCAGON, DOPAMINA