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Editors Selection IGR 9-3

Basic Research: Memantine, hyperbaric oxygen and brimonidine on RGC survival

Comment by Francesca Cordeiro on:

46060 An immunohistochemical analysis of the neuroprotective effects of memantine, hyperbaric oxygen therapy, and brimonidine after acute ischemia reperfusion injury, Yigit U; Erdenoz S; Uslu U et al., Molecular Vision, 2011; 17: 1024-1033

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Using a model of acute IOP elevation/ acute retinal ischemia (ARI; IOP increased to 120 mmHg for 60 mins, with assessment at 21 days) in albino rats, Yigit et al. (920) have investigated effects of systemic memantine (25 mg/ kg for one hour after ARI), hyperbaric oxygen (for nine days after ARI) and topical brimonidine (bd for seven days before ARI), on RGC survival.All treatments were reported as being neuroprotective. However, although results are encouraging, certain issues need to be considered. Most notably the method of RGC counting which used paraffin-embedded retinal cross-sections to estimate total cell number, is not very comprehensive compared to whole retinal mounts and retrograde labeling, even though the investigators have clearly made great efforts in trying to compensate for this by using an optical dissector and fractionator sampling scheme. This method originated from sampling of CNS neurons in brain slices, where it is not possible to perform 'en face' analyses such as in whole retinal mounts. A comparison of this method to, for example, whole mount RGC counting would be very useful, if this is to be taken forward as a technique. Likewise, the use of an apoptotic index based on the staining patterns seen in Figure 4, is also difficult to appreciate. Although the results are very interesting, their relevance is also tempered by the different treatment regimens applied, and more importantly, why each was specifically chosen by the authors. It is also important to recognize that the ARI injury can also cause dysfunction in retinal neurons other than RGCs ‐ indeed the model is increasingly employed for photoreceptor ischemia, yet there is no evidence of this on the histology presented in this paper. In summary, the paper describes a new technique which may be interesting but needs further validation. The influence of sampling errors and staining characteristics is therefore unknown, and thus the encouraging results presented need cautious interpretation.

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