The antidepressant hypericin inhibits progression of experimental proliferative vitreoretinopathy

Purpose. Hypericin, a polycyclic dione used as an antidepressant, has been shown to inhibit the protein kinase C (PKC) pathway. Many of the pathologic responses found in proliferative vitreoretinopathy (PVR) are dependent upo n PKC. Therefore, we studied the effect of hypericin on the treatment of ex perimental PVR. Methods. PVR was induced in pigmented rabbits by intravitreal injection of 50,000 rabbit conjunctival fibroblasts after vitrectomy. Subsequently, the eyes received an intravitreal injection of either balanced salt solution (B SS, 0.1 mL) (group A, control) or hypericin (0.1 mL) in doses of 1 mu M (gr oup B), 10 mu M (group C), and 100 mu M (group D). The eyes were examined o phthalmoscopically on days 1, 3, 7, 14, and 28 after surgery and the stage of PVR was evaluated (0 to V). The effect of hypericin on retinal morpholog y and function was also determined for the eyes injected with 100 mu M hype ricin with no fibroblasts by light microscopy and electroretinogram (ERG). Results. In the control eyes, the retina was detached after 5 days, membran es had formed on and beneath it, and the PVR had progressed to higher stage s over time. In the eyes injected with hypericin, the PVR also progressed; however, the severity of PVR on each day was lower than that in control eye s on that day. PVR was significantly inhibited in groups C and D as compare d with the control eyes after day 5 (P < 0.05). Histological examination of the hypericin-treated control eyes disclosed no morphological change, and ERG analysis revealed no significant functional change. Conclusions. Intravitreal injection of hypericin is a safe and effective me ans of reducing experimental PVR.