A nicotinic acetylcholine receptor agonist prevents loss of retinal ganglion cells in a glaucoma model.

Abstract

PURPOSE:

The purpose of this study was to analyze the neuroprotective effect of an α7 nAChR agonist, PNU-282987, using an in vivo model of glaucoma in Long Evans rats.

METHODS:

One eye in each animal was surgically manipulated to induce glaucoma in control untreated animals and in animals that were treated with intravitreal injections of PNU-282987. To induce glaucoma-like conditions, 0.05 mL of 2 M NaCl was injected into the episcleral veins of right eyes in each rat to create scar tissue and increase intraocular pressure. The left eye in each rat acted as an internal control. One month following NaCl injection, rats were euthanized, retinas were removed, flatmounted, fixed, and nuclei were stained with cresyl violet or RGCs were immunostained with an antibody against Thy 1.1 or against Brn3a. Stained nuclei in the RGC layer and labeled RGCs in NaCl-injected retinas were counted and compared with cell counts from untreated retinas in the same animal.

RESULTS:

NaCl injections into the episcleral veins caused a significant loss of cells by an average of 27.35% (± 2.12 SEM) in the RGC layer within 1 month after NaCl injection, which corresponded to a significant loss of RGCs. This loss of RGCs was eliminated if 5 μL of 100 μM PNU-282987 was injected into the right eye an hour before NaCl injection.

CONCLUSIONS:

The results from this study support the hypothesis that the α7 agonist, PNU-282987, has a neuroprotective effect in the rat retina. PNU-282987 may be a viable candidate for future therapeutic treatments of glaucoma.

• Authors: Kazuhiro Iwamoto, Patrick Birkholz, Austin Schipper, David Mata, David M Linn, Cindy L Linn
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 55 Issue 2 Pg. 1078-87 (Feb 24 2014) ISSN: 1552-5783 [Electronic] United States
• PMID: 24458148 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Bridged Bicyclo Compounds
• Neuroprotective Agents
• Nicotinic Agonists
• PNU-282987
• alpha7 Nicotinic Acetylcholine Receptor

Topics

• Animals
• Benzamides (therapeutic use)
• Bridged Bicyclo Compounds (therapeutic use)
• Cell Count
• Chromatography, High Pressure Liquid
• Disease Models, Animal
• Female
• Glaucoma (chemically induced, pathology, prevention & control)
• Intravitreal Injections
• Male
• Neuroprotective Agents (therapeutic use)
• Nicotinic Agonists (therapeutic use)
• Optic Nerve Diseases (chemically induced, pathology, prevention & control)
• Rats
• Rats, Long-Evans
• Retinal Degeneration (chemically induced, pathology, prevention & control)
• Retinal Ganglion Cells (drug effects, pathology)
• Tandem Mass Spectrometry
• Tonometry, Ocular
• alpha7 Nicotinic Acetylcholine Receptor (agonists)