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Editors Selection IGR 11-3

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Comment by Jeffrey Goldberg on:

24490 Experimental and clinical evidence of neuroprotection by nerve growth factor eye drops: Implications for glaucoma, Lambiasea A; Aloe L; Centofanti M et al., Proceedings of the National Academy of Sciences of the United States of America, 2009; 106: 13469-13474

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Rita Levi-Montalcini has a long, storied history of contributions to neuroscience, particularly to our understanding of neurotrophic factors, starting with nerve growth factor (NGF). Such factors contribute to survival, axon growth, and regeneration in both the developing and degenerating nervous system. NGF in particular was previously shown to protect retinal ganglion cells (RGCs) in models of retinal ischemia (IOVS 34: 3232) and ocular hypertension (Graefes Arch Clin Exp Ophthalmol 235: 780), but maybe not directly after optic nerve trauma (Mol Cell Neurosci 40:410). In the current study (PNAS 106: 13469), NGF similarly saves RGCs from death in a rat glaucoma model. The experiments are done with basic histologic examination, and without the identification of RGCs among the cells in the ganglion cell layer. More striking, the authors administered NGF eye drops to three human glaucoma patients for three months, and reported the visual-field and electroretinogram results pre- and posttherapy. The results are stimulating, suggesting an improvement in VF and PERG metrics, but fraught with interpretative challenges, arising mainly from the small number of patients compared to the high short- and long-term fluctuation variability seen in such measures. Their claim of 'neuroprotection' (saving RGCs from death, not likely a significant contribution of trophic factors in such a short-term study), should probably be conceptualized as 'neuroenhancement', stimulating the remaining RGCs to function more effectively, which could occur by direct or indirect action of NGF.

The major source of frustration from their audience will reflect the publication in an essentially non-peer reviewed format. PNAS has just recently announced that they plan to end the practice of allowing National Academy members like Dr. Levi-Montalcini from 'Communicating' their friends' and colleagues' papers into the journal, but members will still be able to 'Contribute' their own work, as she did here, allowing them to 'subvert peer review' and publish manuscripts of 'dubious' quality or import (Science 325:1486). If this practice must continue, Dr. Levi-Montalcini should collaborate with her National Academy colleagues to better differentiate between their own submissions and the anonymously peer-reviewed papers in their journal. Despite these flaws in the paper and in the journal, Dr. Levi-Montalcini is to be commended for beginning the process of translating basic research findings towards clinical use, and I hope that appropriately designed clinical trials, as recommended at the end of her paper, will follow.

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