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Editors Selection IGR 16-4

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Comment by James Morgan 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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This is a milestone publication in that it demonstrates that nerve growth factor (NGF), given in the form of eye drops, has significant measurable, beneficial effects in glaucoma subjects in terms of visual field, visual acuity, optic nerve function and contrast sensitivity. The article is impressive because of the unique data, its publication in a high-impact, reputable journal and because of the caliber of the authors, one of whom is a Nobel Prize Laureate. I have always supported the premise that neuroprotection in glaucoma is an achievable goal and am therefore delighted by the report.

However, I remain puzzled as to how sufficient NGF might reach the human retina following topical application. Theoretically, this might be achieved by transport via the systemic system or across the sclera. I have difficulty imagining that this is achievable in large animals, but accept that this is possible in small animals like the rat. It is also unclear how single drops of NGF solution were instilled into the fornix of the conjunctiva four times a day over three months in the glaucoma patients to produce these remarkable findings. I accept that topical drugs applied liberally to rats can reach the retina by the systemic system, but it should not be forgotten that the drug might be primarily located to retinal blood vessels. Lambiaseet al. show that sufficient topically applied NGF reaches retinal cells to have a significantly positive effect on the survival of ganglion cells in a rat glaucoma model. However, a scrutiny of the reported data raises some questions. For example, the retinal sections shown in Figures 2B and 2C are clearly from different eccentricities indicated by the variation in the thicknesses of the nuclear layers. This must be born in mind when noting any differences in the numbers of cells in the ganglion cell layer between the two retinal sections. The actual procedure used for determining ganglion cell numbers cannot be described as being optimum, especially since not all cells in the ganglion cell layer are ganglion cells. The staining for TUNELpositive (apoptotic) cells in the ganglion cell layer and their quantification in the rat glaucoma model is not convincing. In conclusion, the results reported by Lambiase et al. are undoubtedly exciting but certainly require corroboration.

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