Short-Term Moderately Elevated Intraocular Pressure Is Associated With Elevated Scotopic Electroretinogram Responses

Abstract

PurposeModerately elevated intraocular pressure (IOP) is a risk factor for open-angle glaucoma. Some patients suffer glaucoma despite clinically measured normal IOPs. Fluctuations in IOP may have a significant role since IOPs are higher during sleep and inversion activities. Controlled transient elevations of IOPs in rats over time lead to optic nerve structural changes that are similar to the early changes observed in constant chronic models of glaucoma. Because early intervention decreases glaucoma progression, this study was done to determine if early physiological changes to the retina could be detected with noninvasive electrophysiological and optical imaging tests during moderately elevated IOP.MethodsIntraocular pressures were raised to moderately high levels (35 mm Hg) in one eye of Sprague-Dawley rats while the other (control) eye was untreated. One group of rats underwent scotopic threshold response (STR) and electroretinogram (ERG) testing, while another 3 groups underwent optical coherence tomography (OCT) imaging, Western blot, or histologic evaluation.ResultsThe amplitudes of the STR and ERG responses in eyes with moderately elevated IOPs were enhanced compared to the values before IOP elevation, and compared to untreated contralateral eyes. Structural changes to the optic nerve also occurred during IOP elevation.ConclusionsAlthough ischemic IOP elevations are well-known to globally reduce components of the scotopic ERG, acute elevation in rats to levels often observed in untreated glaucoma patients caused an increase in these parameters. Further exploration of these phenomena may be helpful in better understanding the mechanisms mediating early retinal changes during fluctuating or chronically elevated IOP.

Isoflurane and ketamine:xylazine differentially affect intraocular pressure-associated scotopic threshold responses in Sprague-Dawley rats

“…1, 3c). These data suggest that the threshold value was unaffected by whether IOP was elevated or not in the eyes and are also similar to the IOP-independent threshold values observed for isoflurane-anaesthetised rats in our previous experiment [16]. In addition to matching the threshold for the pSTRs in our previous study, the pSTRs thresholds in the present study fall within the luminance range used by other investigators [3,5,26].…”

“…While the threshold for isoflurane-anaesthetised rats prior to loop-wear was not as distinct, a clear threshold was observed for these rats during loop-wear (Fig. 2c), and the value of the threshold matched that of our previous study, −4.24 log cd·s/m 2 [16]. This threshold value was also observed for ketamine:xyalazine-anaesthetised rats with and without a loop in the present study (Figs.…”

“…Peak amplitudes and implicit times were measured from STR recordings elicited with flash stimuli greater than −4.24 log scotopic cd·s/m 2 as per Choh et al , [16]. At baseline (prior to any intervention) for each anaesthetic, the pSTR amplitudes for the control and treated eyes were similar (p>0.9999 for all luminance steps; Fig.…”

“…In the present study, high frequencies were retained in the waveforms using standard ERG filtering with an analogue band pass of 0.312 to 300 Hz [24], resulting in more high frequency noise than in previous studies that filtered frequencies above 30 Hz [3,13,16,25]. While the threshold for isoflurane-anaesthetised rats prior to loop-wear was not as distinct, a clear threshold was observed for these rats during loop-wear (Fig.…”

“…Acute ischaemic intraocular pressure (IOP) levels reduce or extinguish STRs [13–15] and other ERG waveforms [13,15]. However, acute, IOP elevation to moderate levels around 35 mmHg is associated with enhanced ERG and STR waveforms, which are extinguished at ischaemic levels (80 mmHg) [16]. These enhanced STR and ERG waveforms were recorded while rats were anaesthetised with isoflurane.…”