In the young, non-glaucomatous retina, Vesl-1S/Homer 1a prevents synaptic coupling of intracellular calcium channels (ICC) in the membranes of the endoplasmic reticulum with G-protein coupled receptors (GPCR) at the plasma membrane, resulting in tightly controlled intracellular Ca2+ release mediated by 2nd messenger pathways (green arrow). Up-regulation of Vesl-1L/Homer 1c in the aged, glaucomatous retina increases synaptic coupling, leading to increased intracellular Ca2+ release due to increased strength of second messenger pathways (red arrow) and the direct modulation of ICCs by Vesl-1L/Homer 1c.