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Editors Selection IGR 11-1

Basic Research: Retinal ganglion cell protection

Comment by James Morgan on:

24165 Transplanted oligodendrocyte precursor cells reduce neurodegeneration in a model of glaucoma, Bull ND; Irvine KA; Franklin RJ et al., Investigative Ophthalmology and Visual Science, 2009; 50: 4244-4253

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Bull et al. (1007) presents data on the use of oligodendrocyte precursor cells (OPC) in the protection of retinal ganglion cells in a rodent model of experimental glaucoma. The paper raises several interesting issues concerning methods for the protection of retinal ganglion cells in oculohypertensive eyes. The principle findings of the study are twofold. Firstly, that OP cells can survive for long periods of time (up to 12 weeks) following intravitreal injection, showing some limited integration with the underlying retina. Secondly, that their protective effect is only apparent following activation with Zymosan, a pro-inflammatory agent. The study is well designed and offers a thorough assessment of the challenges and opportunities that are to be met with the use of neural cell replacements for the protection of the retina in glaucoma. The rescue in the RGC population, is modest but significant, improving axon survival from just over 50 to 70%. The study provides an important platform for considering the use of stem cells/OPC cells in the mitigation of retinal ganglion cell death but also raises many questions about the use of these cells. The use of a cell line for the delivery of neurotrophins seems appropriate. The difficulties in getting cells to integrate with the underlying retina highlight the limitations in the use of these models for the restoration of neural function by the replacement of lost cells. The use of replacement cells for the delivery of supportive molecules seems more appropriate. Yet it is clear that considerable work is required before we can consider these as possible treatments. As the cells tend to reside on the retinal surface the possibility remains that they will incite a glial response that will adversely affect the quality of vision ‐ it is important to note that the functional effects of the use of OPC cells have yet to be determined. The authors have excluded a direct effect of microglial/ astrocyte response to Zymosan as having a neuroprotective effect ‐ but further work is required to exclude the possibility that these cells do not play a role in mediating protection in Zymosan-treated OPCs. The study highlights some of the difficulties in working with animal models of glaucoma. The IOPs showed considerable swings between laser treatments and while significant differences did not exist within the groups, it is not clear whether this was the case between treatment groups between the various experiments. The study is valuable is showing the viability of OP cells in the retina but also reveals the difficulties in ensuring integration in the underlying substrate. Longer survival times are required to rule out any detrimental effects of OP cells and to determine that any protective effect is persistent (rather than a delay in the process of cell loss). The final arbiter of success with these experiments would be the demonstration that visual function in preserved compared with untreated eyes.

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