The antidepressant hypericin inhibits progression of experimental proliferative vitreoretinopathy.
OBJECTIVE
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 upon PKC. Therefore, we studied the effect of hypericin on the treatment of experimental 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 (BSS, 0.1 mL) (group A, control) or hypericin (0.1 mL) in doses of 1 muM (group B), 10 muM (group C), and 100 muM (group D). The eyes were examined ophthalmoscopically 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 morphology and function was also determined for the eyes injected with 100 muM hypericin with no fibroblasts by light microscopy and electroretinogram (ERG).


RESULTS
In the control eyes, the retina was detached after 5 days, membranes had formed on and beneath it, and the PVR had progressed to higher stages 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 eyes on that day. PVR was significantly inhibited in groups C and D as compared 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 means of reducing experimental PVR.
Tahara
Y R
YR
Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Sakamoto
T R
TR
Oshima
Y R
YR
Ishibashi
T R
TR
Inomata
H R
HR
Murata
T R
TR
Hinton
D R
DR
Ryan
S J
SJ
D000818:Animals; D000873:Anthracenes; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003228:Conjunctiva / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D005347:Fibroblasts / Q000473:pathology; D007267:Injections; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000502:physiology; D014821:Vitrectomy; D018630:Vitreoretinopathy, Proliferative / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D000873:Anthracenes; D000928:Antidepressive Agents; D010569:Perylene; C004965:hypericin; D011493:Protein Kinase C