Destruction of Müller cells in the adult rat by intravitreal injection of d,l-α-aminoadipic acid. An electron microscopic study

Pedersen, Olav Öyvind; Karlsen, R. Lund

doi:10.1016/0014-4835(79)90044-7

Cited by 67 publications

(38 citation statements)

References 6 publications

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“…No apparent changes were observed in any other cellular elements of the retina other than Müller cells and astrocytes. These results are consistent with previous reports, 17,18,27 which demonstrated that aminoadipic acid at low concentrations caused selective damage to Müller cells and astrocytes without significant effects on the ganglion cells. The implicit time of the ERG b-wave was not prolonged significantly after LAA injections despite the changes of Müller cells and astrocytes.…”

Section: Discussionsupporting

confidence: 94%

“…Since Olney et al 16 described its selective effect on Müller cells after subcutaneous administration of DL-a-aminoadipic acid to infant mice, there have been several reports suggesting the specific effect on glial cells by intravitreal injection of LAA. 17,18 In this study, we measured the time course of changes in ONH blood flow in response to elevated IOP by laser speckle flowgraphy (LSFG) to examine the autoregulatory mechanism and also investigated the effects of LAA on the autoregulation. Furthermore, the effects of LAA on glial cells and neurons were verified using electroretinograms (ERGs) and both histologic and immunohistochemical examinations.…”

Section: Purposementioning

confidence: 99%

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

Shibata

Sugiyama²,

Kurimoto³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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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.

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Section: Discussionsupporting

confidence: 94%

Section: Purposementioning

confidence: 99%

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

Shibata

Sugiyama²,

Kurimoto³

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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“…Second, the current results did not determine which retinal glial cells, the Müller glial cells or astrocytes, play a central role in retinal circulation in response to flicker stimulation, because it is difficult to suppress separately each cellular function using a gliotoxic compound that affects both of them. 19,20 Third, although the current data did not provide a definitive explanation for the effect of general anesthesia, we previously found in a preliminary study that sevoflurane per se did not change the vessel D of isolated porcine retinal arterioles (data not shown) and the changes in the concentration of pancuronium bromide did not alter the RBF in cats anesthetized with sevoflurane (data not shown). 26 Finally, we could not investigate to what degree the retinal glial cells contributed to the basal RBF, because it is difficult to quantify the degree of functional damages in the retinal glial cells after intravitreal injection of LAA at a concentration of 60 mM.…”

Section: Discussioncontrasting

confidence: 59%

“…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. 19,20 In fact, a recent immunohistochemistry evaluation found that LAA at a concentration of 60 mM damaged the retinal glial cells, histologic evaluation showed intact neural cells, and there was no significant reduction of the ERG b-wave. 17 In addition, we also determined whether 60 mM of LAA injected intravitreally may have any toxic effects on the neurons, which was confirmed by ERG and histologic examination in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Song

Nagaoka

Yoshioka

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To investigate how glial cells participate in retinal circulation during flicker stimulation in cats.METHODS. Using laser Doppler velocimetry, we measured the vessel diameter and blood velocity simultaneously and calculated the retinal blood flow (RBF) in feline first-order retinal arterioles. Twenty-four hours after intravitreal injections of L-2-aminoadipic acid (LAA), a gliotoxic compound, and the solvent of 0.01 N hydrochloric acid as a control, we examined the changes in RBF in response to 16-Hz flicker stimulation for 3 minutes. We also measured the changes in RBF 2 hours after intravitreal injection of Nx-propyl-L-arginine (L-NPA), a selective neuronal nitric oxide synthase inhibitor, in LAA-treated eyes. To evaluate the effects of LAA on retinal neuronal function, ERGs were monitored. Immunohistochemical examinations were performed.RESULTS. In LAA-treated eyes, histologic changes selectively occurred in retinal glial cells. There were no significant reductions in amplitude or elongation of implicit time in ERG after LAA injections compared with controls. In control eyes, the RBF gradually increased and reached the maximal level (53.5% 6 2.5% increase from baseline) after 2 to 3 minutes of flicker stimulation. In LAA-treated eyes, the increases in RBF during flicker stimulation were attenuated significantly compared with controls. In LAA-treated eyes 2 hours after injection of L-NPA, flicker-evoked increases in RBF decreased significantly compared with LAA-treated eyes. CONCLUSIONS.The current results suggested that increases in RBF in response to flicker stimulation were regulated partly by retinal glial cells.

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Selective ablation of astrocytes by intracerebral injections of ?-aminoadipate

Khurgel

Koo

Ivy

1996

Glia

103

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Destruction of Müller cells in the adult rat by intravitreal injection of d,l-α-aminoadipic acid. An electron microscopic study

Cited by 67 publications

References 6 publications

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

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

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

Selective ablation of astrocytes by intracerebral injections of ?-aminoadipate

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