4.0 Article

Multifocal electroretinography increases following experimental glaucoma in nonhuman primates with retinal ganglion cell axotomy

Journal

DOCUMENTA OPHTHALMOLOGICA
Volume 146, Issue 2, Pages 97-112

Publisher

SPRINGER
DOI: 10.1007/s10633-023-09922-1

Keywords

Experimental glaucoma; Axotomy; Multifocal electroretinography; Supranormality

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Through the study of multifocal electroretinography (mfERG) in experimental glaucoma (EG), it was found that short-latency changes may be related to both retinal ganglion cell (RGC) loss and elevated intraocular pressure (IOP).
PurposeTo determine whether short-latency changes in multifocal electroretinography (mfERG) observed in experimental glaucoma (EG) are secondary solely to retinal ganglion cell (RGC) loss or whether there is a separate contribution from elevated intraocular pressure (IOP).MethodsPrior to operative procedures, a series of baseline mfERGs were recorded from six rhesus macaques using a 241-element unstretched stimulus. Animals then underwent hemiretinal endodiathermy axotomy (HEA) by placing burns along the inferior 180 degrees of the optic nerve margin in the right eye (OD). mfERG recordings were obtained in each animal at regular intervals following for 3-4 months to allow stabilization of the HEA effects. Laser trabecular meshwork destruction (LTD) to elevate IOP was then performed; first-order kernel (K1) waveform root-mean-square (RMS) amplitudes for the short-latency segment of the mfERG wave (9-35 ms) were computed for two 7-hexagon groupings-the first located within the superior (non-axotomized) macula and the second within the inferior (axotomized) macula. Immunohistochemistry for glial fibrillary acidic protein (GFAP) was done.ResultsBy 3 months post HEA, there was marked thinning of the inferior nerve fiber layer as measured by optical coherence tomography. Compared with baseline, no statistically significant changes in 9-35 ms K1 RMS amplitudes were evident in either the axotomized or non-axotomized portions of the macula. Following LTD, mean IOP in HEA eyes rose to 46 +/- 9 compared with 20 +/- 2 mmHg (SD) in the fellow control eyes. In the HEA + EG eyes, statistically significant increases in K1 RMS amplitude were present in both the axotomized inferior and non-axotomized superior portions of the OD retinas. No changes in K1 RMS amplitude were found in the fellow control eyes from baseline to HEA epoch, but there was a smaller increase from baseline to HEA + EG. Upregulation of GFAP in the Muller cells was evident in both non-axotomized and axotomized retina in eyes with elevated IOP.ConclusionsThe RMS amplitudes of the short-latency mfERG K1 waveforms are not altered following axotomy but undergo marked increases following elevated IOP. This suggests that the increase in mfERG amplitude was not solely a result of RGC loss and may reflect photoreceptor and bipolar cell dysfunction and/or changes in Muller cells.

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