Protection of photoreceptors by intravitreal injection of the Y-27632 Rho-associated protein kinase inhibitor in Royal College of Surgeons rats

Retinitis pigmentosa (RP) is an inherited retinal disease, which is characteristic by degeneration of the rod and cone photoreceptors. The present study aimed to assess the protective effects on photoreceptors of intravitreal injection of Y-27632, a specific inhibitor of Rho-associated protein kinase (ROCK), in a Royal College of Surgeons (RCS) rat model. Different concentrations of Y-27632 (1-50 mM) were administered by intravitreal injection into the RCS rats. The effects of Y-27632 were recorded using electroretinography (ERG), measuring the thicknesses of the retinal outer nuclear layer (ONL) and examination of apoptotic markers using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and western blot analysis. Treatment of the eyes with Y27632 at 10 or 50 mM, led to a 30% increase in a-and b-wave amplitudes in ERG, and an increase in ONL thickness by 10%, compared with the 1 mM Y-27632-treated and vehicle (phosphate-buffered saline; PBS)-treated groups. In addition, eyes treated with 10 mM Y27632 exhibited a 90% decrease in TUNEL-positive cells, accompanied by decreased protein expression levels of active caspase 3 and Bax by 50%, and a 90% increase in the ratio of Bcl-2/Bax, compared with the PBS-treated groups. These data suggested that Y-27632 protected retinal function by inhibiting the apoptosis of photoreceptor cells in the RCS rat model. The present study demonstrated for the first time, to the best of our knowledge, to report the use of Y-27632 for protection against RP in an RCS rat model. Y-27632 may be a potential candidate for the treatment of human RP.