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Cindy L. Linn, Kacuhiro Iwamoto, Patrick J. Birkholz, David M. Linn; Glaucoma-induced Cell Loss In The Retinal Ganglion Cell Layer Can Be Prevented Using Nicotine And The alpha7 nAChR Specific Agonist, PNU-282987. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6674.
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© ARVO (1962-2015); The Authors (2016-present)
To analyze the neuroprotective effect of the ACh agonist, nicotine, and the alpha7 nAChR specific agonist, PNU-282987 in an in-vivo model of glaucoma.
Various treatments were introduced to adult Long Evans rats to get nicotine or PNU-282987 to the retina. Nicotine was applied systemically using nicotine transdermal patches (0.8 or 0.08 mg), by intravitreal injection (5 µl of 100 µM) and by using eye drops (100-200 µM). PNU-282987 was applied by intravitreal injection (5 µl of 100 µM). Following treatments with nicotine or PNU-282987, surgery was performed to induce glaucoma by injecting 0.5 ml of 2 mM NaCl into the episcleral veins of the right eye in each rat according to the procedure described by Morrison et al., (1997). The left eye in each rat was left untreated. After one month, the rats were euthanized. The retinas were then removed, flat mounted, fixed and nuclei were stained with Cresyl Violet. Stained nuclei in the RGC layer in glaucoma-induced retinas were counted and compared to cell counts from untreated retinas.
One month following hypertonic saline injection, there was significant loss of cells in the RGC layer compared to untreated conditions (average loss of 28% +/- 5). However, cell death decreased to 0% if rats were treated systemically with 0.8 mg nicotine patches, if 100 µM nicotine or PNU-282987 was injected into the vitreous humor, or if 200 µM nicotine was applied as eye drops before inducing glaucoma. In fact, when eyes were treated with 200 µM nicotine eye drops or when 100 µM nicotine or PNU 282987 was injected into the vitreous humour before inducing glaucoma, there was a significant increase in cell counts (average of 9% (+/- 3) compared to the untreated retina. However, eye drops containing 100 µM nicotine did not protect against cell loss in the RGC layer as there was a decrease of 19% (+/- 3) cells in the RGC layer when compared to the untreated control. In sham experiments, PBS was injected into the vitreous humour before inducing glaucoma. Under these conditions, there was a 25% loss of cells in the RGC layer compared to untreated conditions.
These results support the hypothesis that hypertonic saline injections into the episcleral vein can be used as a robust in-vivo model of glaucoma and that nicotine and PNU-282987 prevent cell loss from the retinal ganglion cell layer under glaucoma-like conditions. PNU-282987 may be a viable candidate for future therapeutic treatment of glaucoma.
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