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Editors Selection IGR 18-2
Animal Models: Neuroprotection
Comment by Benjamin J. Frankfort on:
70413 Reversal of functional loss in a rat model of chronic intraocular pressure elevation, Liu HH; He Z; Nguyen CT et al., Ophthalmic and Physiological Optics, 2017; 37: 71-81
A recent paper by Liu et al., 'Reversal of functional loss in a rat model of chronic intraocular pressure elevation', used the circumlimbal suture method of IOP elevation to assess retinal electrical activity (using ERG) and retinal anatomy (using OCT) at multiple time points in seven male Long- Evans rats. IOP was elevated in one eye of each experimental animal for eight weeks, leaving the fellow eye as a control (mean IOP = 21.9 mmHg for experimental eyes and 12.5 mmHg for control eyes). After eight weeks, the circumlimbal suture was released to return IOP to normal for an additional seven weeks (mean IOP = 12.9 mmHg for experimental eyes and 11.5 mmHg for control eyes). This approach allowed the authors to look for functional and anatomic recovery following return to normal IOP levels.
These data suggest that some recovery of RGC electrical function is possible, despite cellular injury as indicated by the persistent reduction of RNFL thickness
The amplitude of the positive scotopic threshold response (pSTR), an indicator of retinal ganglion cell (RGC) electrical activity, was reduced by IOP elevation to 75% of baseline at week eight and then recovered to nearly baseline levels (96%) by the end of the study, whereas the thickness of the retinal nerve fiber layer (RNFL) decreased to about 90% of baseline by week eight and did not recover. The pSTR correlated positively with RNFL thickness.
These results have important implications for glaucoma. Firstly, these data suggest that some recovery of RGC electrical function is possible, despite cellular injury as indicated by the persistent reduction of RNFL thickness. This may be akin to a pre-clinical phase of glaucoma in which RGCs and their axons are stressed but still can return to relatively normal activity if IOP is treated. While not studied in this manuscript, given the finding that the pSTR was correlated with the RNFL, it would be very interesting to see if the more severely impacted eyes lost visual function, as measured via a behavioral test such as an optokinetic response, since it is possible that the electrical activity of the RGC layer is not effectively communicated to the brain due to the abnormal RNFL. Secondly, these data confirm that it is possible to model reversible IOP-related RGC injury in rodents, thus opening the door for further studies (assessing the impact of novel and existing treatments, for example).
It is important to note that the number of animals in this study was small and all experimental animals were male. It will be necessary to expand these and similar studies in both number and gender to ensure that the results can be generalized.
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