Purchase this article with an account.
G.–M. Sarra, S. Eigeldinger–Berthou, P. Trittibach, C. Meier, A.D. Olac–Gaona, S. Wolf; Photoreceptor–Cell Rescue After Treatment With a Novel 2nd Generation Propargylamine (Rasagiline) in the RDS–Mouse Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4562.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Rasagiline mesylate is a novel second–generation monoamine oxidase type B (MAO–B) inhibitor, which also excerts dose–dependent neuroprotective effects, mediated by expression of anti–apoptotic proteins (Bcl–2 and protein–kinase–C) and downregulation of pro–apoptotic proteins (Bad and Bax). Here we analyse the neuroprotective effect of rasagiline on the photoreceptor cells (prc) in the retinal degeneration slow (rds) mouse.
In total 10 rds mice were treated daily, from P1 up to P56: 5 mice received 2 µg rasagiline per gram of body weight orally, 5 were injected 6 out of 7 days with 10 µg rasagiline per gram of body weight subcutaneously once a day. Adequate numbers of age matched untreated controls were used. The right eyes were subjected to morphometric analysis using semithin sections, the left eyes were fixed in PFA 4% and frozen for cleaved caspase–3 immunohistochemistry. MAO–B inhibition assays of frozen brain tissue were used to analyze rasagiline availability in the CNS.
Rasagiline was well tolerated even in newborn pups. MAO–B inhibition in the brain was at least 97% in all treated animals, suggesting a sufficient bioavailability in the CNS and the retina. Oral and subcutaneous treatment with rasagiline resulted in a significant rescue (18.2% and 12.5%) of prc compared to untreated animals (p=0.0001 and 0.001; Mann–Whitney U test). This effect correlated with a reduction of cleaved caspase–3 positive prc at P16 in the two treatment groups.
Rasagiline appears to reduce prc apoptosis through a caspase–3 dependent pathway in the rds mouse. This is in line with previous studies that have shown a substantial rescue of prc in the rds mouse by transgenic overexpression of Bcl–2. The present study provides first evidence for a putative role of rasagiline in the treatment of human retinal disease such as retinitis pigmentosa.
This PDF is available to Subscribers Only