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Editors Selection IGR 7-3

Basic science: NGF as neuroprotectant

Martin Wax

Comment by Martin Wax on:

13176 Pharmacokinetics of conjunctivally applied nerve growth factor in the retina and optic nerve of adult rats, Lambiase A; Tirassa P; Micera A et al., Investigative Ophthalmology and Visual Science, 2005; 46: 3800-3806


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Growth factors of the neurotrophin (NGF, BDNF, etc.) and the GDNF (GDNF, neurturin, etc.) families are critically important in the development and maintenance of neural cells, including retinal neurons. They also have been shown to be remarkably potent as neuroprotectants in several in vitro and in vivo models of neurodegeneration. But since they are large polypeptides with molecular sizes in the range of thousands of Daltons, can they be used as drugs to treat neurodegenerative disorders such as glaucoma or AMD using conventional delivery techniques? The work of Lambiase et al. (1064) indicates that this may be possible. These investigators delivered NGF topically to the conjunctival fornix, 0.1, 2, or 5 mg, in 10 ml of saline. Remarkably, increases in immunoreactive NGF were detected in retina, optic nerve, and serum within two h, peaked at six h and persisted for 24 h. The peak levels achieved (~4 ng/retina) seem to be high enough to exert effects. Indeed, an increase in retinal expression of BDNF mRNA and protein was observed in the ipsilateral, but not the contralateral, eyes.

These findings encourage studies to answer the next logical questions to ask. Is this ability to penetrate unique to NGF (an unusually basic protein) or will other neurotrophic factors also 'get in'? And more provocatively, does topical application of NGF lead to demonstrable neuroprotective efficacy in a disease model?


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