Using DARC to assess neuroprotection of a systemic Abeta modulator in a glaucoma model

Abstract

Several lines of evidence suggest that there are similarities in the pathomechanisms of glaucoma and Alzheimer’s disease, and that amyloid-beta (Ab) could be a new, promising target for neuroprotective therapy of glaucoma. In the present study, we evaluated the effect of the Ab 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 Ab were reached. Hence the present results are consistent with the notion that Ab is a promising target for neuroprotective intervention in glaucoma and that MRZ-99030 may be a good drug candidate for further development.