title: Effect of the Aβ aggregation modulator MRZ-99030 on retinal damage in an animal model of glaucoma.
abstract: Several lines of evidence suggest that there are similarities in the pathomechanisms of glaucoma and Alzheimer's disease, and that amyloid-beta (Aβ) could be a new, promising target for neuroprotective therapy of glaucoma. In the present study, we evaluated the effect of the Aβ aggregation modulator MRZ-99030 in the Morrison model of glaucoma based on increased intraocular pressure (IOP) in rats. MRZ-99030 provided dose-dependent neuroprotection and at the highest dose (240 mg/kg) reduced the degree of RGC apoptosis to 33 % of that seen after vehicle (P < 0.05; one-way ANOVA). No significant effect on IOP was observed. Pharmacokinetic experiments showed that following systemic injection of MRZ-99030, concentrations above affinity for Aβ were reached. Hence the present results are consistent with the notion that Aβ is a promising target for neuroprotective intervention in glaucoma and that MRZ-99030 may be a good drug candidate for further development.
authors.affiliation: Visual Neuroscience, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK.
authors.forename: T E
authors.initials: TE
authors.lastname: Salt
authors.forename: S
authors.initials: S
authors.lastname: Nizari
authors.forename: M F
authors.initials: MF
authors.lastname: Cordeiro
authors.forename: H
authors.initials: H
authors.lastname: Russ
authors.forename: W
authors.initials: W
authors.lastname: Danysz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: C000598750:2-(2-amino-3-(1H-indol-3-yl)propionylamino)-2-methylpropionic acid; D004151:Dipeptides; D018696:Neuroprotective Agents
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