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Editors Selection IGR 11-2

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Comment by Leonard A. Levin 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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Neuroprotection is a dream therapy, not only for our glaucoma specialists, but for all neurology clinicians. The eye is an ideal candidate to try and develop the neuroprotective drugs compared to the other neuronal system such as a brain, because we have tools to assess and evaluate neurodegeneration quantitatively by both function and structure. NGF is a classic neurotrophic factor binding to TrkA receptor expressing RGC and other neuronal cells. Lambiase et al. wrote an interesting paper, showing that NGF eye drops prevent pressure-induced RGC death in a rat glaucoma model by hypertonic saline injection, and in a human model with end-stage glaucoma. NGF eye drops (200µg/ml) QID prevented RGC death in the rat and amazingly improved the glaucoma patient functionally. Previously, Lambiase and colleagues published several fundamental papers as to the biologically sufficient penetration of NGF eye drops into the retina.

My concerns are as follows. RGC death was histologically evaluated by retinal section, but the retrograde labeling method to count RGCs is recommended for accuracy. The background of TUNELstaining in an ocular hypertensive rat retina is much higher compared to the control and NGF treated retina (figs. 3B and 4D). Thus, apoptosis induced by ocular hypertension is pretty obscure in these data. In the human study, a comparative study with control patients and increased number of patients should be conducted to obtain the robust evidence by excluding a placebo effect especially in the human visual field test. In this study, two different situations of RGC death were mixed. One is acute RGC damage by excessive pressure, and the other is chronic RGC damage by mild IOP elevation. Thus, the role of NGF in both conditions may be different. The former is a protective role and the latter is a regenerative role. In this point, NGF is a dreamlike agent for neuroprotection and neuroregeneration. Future tests in a multicenter study should be conducted to verify the hopeful outcome of this study.

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