Involvement of Glial Cells in the Autoregulation of Optic Nerve Head Blood Flow in Rabbits

Abstract

PURPOSE.To investigate the involvement of glial cells in the autoregulation of optic nerve head (ONH) blood flow in response to elevated intraocular pressure (IOP).METHODS. Rabbit eyes were treated with an intravitreal injection of L-2-aminoadipic acid (LAA), a gliotoxic compound. Twenty-four hours after the injection IOP was artificially elevated from a baseline of 20 to 50 or 70 mm Hg and maintained at each IOP level for 30 minutes. ONH blood flow was measured by laser speckle flowgraphy every 10 minutes. Ocular perfusion pressure (OPP) was calculated to investigate the relationship between ONH blood flow and OPP. To evaluate the effects of LAA on the function and morphology of retinal neurons and glial cells, electroretinogram (ERG) was monitored after injections of LAA (2.0 and 6.0 mM) or saline as a control. Histologic and immunohistochemical examinations were then performed.RESULTS. In the LAA-treated eyes, histologic changes selectively occurred in the retinal Müller cells and ONH astrocytes. There was not any significant reduction of amplitude or elongation of implicit time of each parameter in the ERG after LAA injection compared with control. ONH blood flow in LAA-treated eyes was significantly decreased with a reduction of OPP during IOP elevation to 50 and 70 mm Hg, whereas blood flow was maintained in control eyes during IOP elevation to 50 mm Hg. CONCLUSIONS.These results indicate the involvement of glial ells in the autoregulation of ONH blood flow during IOP elevation. (Invest Ophthalmol Vis Sci.

Role of Glial Cells in Regulating Retinal Blood Flow During Flicker-Induced Hyperemia in Cats

“…Indeed, another previous report showed that LAA at a concentration of 200 mM caused neural damage and significantly affected the ERG b-wave at 24 hours in rabbits. 17 In our preliminary experiment, we also confirmed that LAA at a concentration of 200 mM caused a significant reduction in the amplitude of the ERG b-wave in cats (data not shown). However, some reports have suggested that the implicit time of the ERG b-wave was not prolonged significantly after injections of low concentrations of LAA despite changes in the Müller cells and astrocytes.…”

“…27 The 24-hour time course after intravitreal injection of LAA was chosen because pathologic changes and dysfunction on the ERGs were not observed in the neural retina, although the Müller cells had some damage, that is, pale stained nuclei and increased glycogen granules 24 hours after the LAA injections. 17,27 Changes in RBF to Flicker Stimulation…”

“…[13][14][15] However, the involvement of glial cells in regulating the RBF in response to flicker stimulation has not been well determined. 16 Although some reports have focused on the role of glial cells in metabolic autoregulation in neurovascular coupling, 2,6,[16][17][18] the role in the retinal vasculature remains unclear.…”

“…In previous studies, L-2-aminoadipic acid (LAA), 17,19,20 a gliotoxic compound, was injected intravitreally to examine the specific role of glial cells in the retina. We investigated the role of retinal glial cells in regulating the RBF in response to flicker stimulation after suppressing the retinal glial cell function with intravitreal injection of LAA in cats.…”

Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation during Isometric Exercise in Healthy Humans

“…Studies supporting the autoregulatory capacity have been performed in healthy humans, nonhuman primates, cats, and rabbits. [17][18][19][20][21][22][23][24][25] The mechanisms that mediate this autoregulatory response in the ONH are unclear. Nitric oxide (NO) is a potent vasodilator that is involved in the maintenance of basal vascular tone, in tonic blood pressure regulation, and in the distribution of blood flow.…”