OBJECTIVE: Parstatin, the N-terminal 41-amino-acid peptide cleaved by thrombin from protease-activated-receptor 1, was shown to be highly effective in preventing ocular angiogenesis and as such it has potential therapeutic applications in ocular neovascular diseases. In the frame of a safety program in preclinical development, we investigated whether parstatin exerts any cytotoxic effect in critical ocular cell populations.
MATERIALS AND METHODS: Human retinal pigment epithelium cell-19 line (ARPE-19) and the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) colorimetric assay were used to investigate parstatin’s effect in cell cultures. Parstatin 24-41 was used as a control peptide which lacks the hydrophobic domain to demonstrate the specificity and the structure-dependent effect of parstatin. Both peptides were used at concentrations ranging from 0.1-30 μM for 24, 48 and 72 hours.
RESULTS: In the presence of parstatin the rate of ARPE-19 cell growth and viability were significantly decreased in a concentration-dependent and time-dependent manner, with an IC50 of approximately 10 μM. When ARPE-19 cells were treated with parstatin 24-41 no inhibitory effect was observed at any concentration or exposure time used.
CONCLUSIONS: Parstatin has a clear detrimental effect on the viability of ARPE-19 cells and raises concerns about its use in the eye because of its possible toxic effects.Free PDF Download
To cite this article
P.S. Gartaganis, M. Cotsiki, E.D. Anastassiou, N.E. Tsopanoglou, M.D. Melachrinou
Parstatin inhibits viability of human retinal pigment epithelium cells: an in vitro cytotoxicity study
Eur Rev Med Pharmacol Sci
Vol. 24 - N. 9