Ocular hypertension is a negative process that occurs within the eye and is the main risk factor to develop glaucoma, a progressive loss of vision due to degeneration of retinal ganglion cells. The protein transduction technique allows a cargo to cross biological membranes. Using this technique we have previously shown that a membrane permeable version of profilin I (PTD4-profilin) increased aqueous humour outflow facility. Here we have investigated if a topical application of PTD4-profilin was able to modify intraocular pressure in rabbits. 10 mu M PTD4-profilin (10 mu L), reduced intraocular pressure by 20% compared to the control vehicle, this value being in the range of other commercial drugs, which produced intraocular pressure reductions between 18 and 35%. The mean-time effect for PTD4-profilin was 6.8 h and was also in the same range as commercial products that provided values between 4.3 and 5.5 h. According to the results presented here we propose PTD4-profilin as a new approach for the treatment of ocular hypertension and PTD4 as a new strategy to facilitate the penetration of molecules into the eye. (c) 2007 Elsevier B.V. All rights reserved.