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A. Di Polo, M. Almasieh, Y. Zhou; Galantamine: A Novel Neuroprotective Strategy For Injured Retinal Ganglion Cells In Glaucoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2699.
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Treatments for glaucoma, currently limited to drugs or surgery to lower intraocular pressure (IOP), are often inefficient. Galantamine is a drug approved by the U.S. Food and Drug Administration and many other jurisdictions for the treatment of Alzheimer’s disease. Galantamine is a modest acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. Galantamine has few side effects and is taken orally by patients. Here we tested if systemic administration of Galantamine resulted in retinal ganglion cell (RGC) neuroprotection in experimental glaucoma.
Unilateral and chronic elevation of intraocular pressure was induced by injection of hypertonic saline solution into an episcleral vein (Morrison model). IOP from glaucomatous and normal (contralateral) eyes was measured daily in awake animals using a calibrated tonometer. Rats received daily intraperitoneal injections of Galantamine (3.5 mg/kg) dissolved in sterile saline solution. Treatment began on the first day of IOP increase and continued thereafter for the entire duration of the experiment. For RGC density quantification, DiI–labeled neurons were counted in 12 standard retinal areas. RGC axons were counted in optic nerve semi–thin cross sections. Counts were performed in duplicate and in a masked fashion.
Our results demonstrate that daily systemic treatment with Galantamine resulted in striking protection of RGCs from ocular hypertension damage. Galantamine treatment led to higher neuronal densities and better preservation of cellular integrity in glaucomatous eyes compared to vehicle–treated controls. In animals with pressure increase (ΔIOP) between 5–10 mm Hg, Galantamine preserved 90% of RGCs at 5 weeks after ocular hypertension surgery (n=10) compared with 65% of RGCs that survived in control eyes (n=7). A pronounced neuroprotective effect of Galantamine was also observed in a group of animals with higher IOP (ΔIOP= 10–20 mm Hg, n=14). Quantification of RGC axons demonstrated that Galantamine protected a significant number of axons in the optic nerve at 5 weeks after ocular hypertension surgery. Systemic Galantamine treatment did not lower IOP, thus the neuroprotective effect of this drug cannot be attributed to IOP reduction.
Our data provide the first demonstration of the clinical potential of Galantamine as neuroprotective therapy for glaucoma and other optic neuropathies. Galantamine has several competitive advantages including good safety profile and excellent drug pharmacokinetics.
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