In previous reports, morphologic changes and activation of glial cells in human glaucoma,
15 experimental glaucoma,
14,27,33 and experimental diabetes
34 were demonstrated. Astrocyte reactivation may be a primary cellular response triggered by elevated IOP or ischemia and/or a secondary cellular response triggered by axonal degeneration.
14 The cell processes of astrocytes are connected to each other via gap junctions,
35,36 which are built mainly of connexin43. These form a functional syncytium that allows astrocytes to communicate and maintain control of the ionic and metabolic homeostasis in the ONH. It was reported that astrocytes in the ONH decrease gap junction communication under conditions of elevated IOP.
37 Closure of gap junctions will interrupt the continuity of astrocyte intercellular communication, causing loss of cell–cell contact and loss of homeostatic regulation.
38 Actually we have already reported that disruption of gap junctions may be involved in the impairment of autoregulation in ONH blood flow.
39 Astrocytes have been shown to participate in blood flow regulation at the gliovascular interface in accordance with neuronal activities in the central nervous system, where astrocytic network couplings with gap junctions surround the vessel walls.
40–42 Neuronal activity evokes localized changes in blood flow in the central nervous system, which is termed neurovascular coupling. Regarding eyes, it has been reported that glial cells also contribute to this neurovascular coupling through gap junctions.
43–45 Another study using LSFG previously reported that a calcium channel antagonist impaired autoregulation of ONH circulation after an acute increase in IOP.
31 It suggested the influx of Ca
2+-related vascular smooth muscle relaxation may also play a role in the autoregulation, even though neurovascular coupling, glial cells, and gap junction are intact. Nevertheless, we speculate that glial cells may have a crucial role in the autoregulation of ONH blood flow through gap junctions, based on the current and the above-cited studies.
40–45