Effect of the Aβ aggregation modulator MRZ-99030 on retinal damage in an animal model of glaucoma

Neurotox Res. 2014 Nov;26(4):440-6. doi: 10.1007/s12640-014-9488-6. Epub 2014 Aug 9.

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.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Dipeptides / pharmacokinetics
  • Dipeptides / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glaucoma / drug therapy*
  • Glaucoma / pathology
  • Glaucoma / physiopathology
  • Intraocular Pressure / drug effects
  • Male
  • Neuroprotective Agents / pharmacokinetics
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Retina / drug effects
  • Retina / pathology
  • Retina / physiopathology

Substances

  • 2-(2-amino-3-(1H-indol-3-yl)propionylamino)-2-methylpropionic acid
  • Dipeptides
  • Neuroprotective Agents