Testing intravitreal toxicity of rapamycin in rabbit eyes.
OBJECTIVE
To evaluate retinal toxicity of varying doses of rapamycin when injected intravitreally in rabbits. Rapamycin is a potent immunosuppressive agent with significant antitumor and antiangiogenic properties, clinically approved for prevention of organ transplant rejection.


METHODS
Twelve New Zealand albino rabbits were divided into four groups. Four different doses of rapamycin were prepared in 0.1 ml: 20 microg, 50 microg, 200 microg, and 1000 microg. Each concentration was injected in one eye of three rabbits, and 0.1 ml volume of sterile BSS was injected into the contralateral eye of the three rabbits. Slit-lamp and fundoscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, and toxicity. A baseline ERG was performed before drug treatment and at day 14, after which the rabbits were euthanized. Histology of the enucleated eyes was studied to look for retinal toxicity.


RESULTS
ERG results showed some decrease in scotopic response; however this was not dose related. ERG results were normal at 20 microg. Histological results showed no retinal toxicity in all groups.


CONCLUSIONS
Although ERG changes were identified at dosages between 50-1000 microg, the histology of all groups up to 1000 microg did not show any discernable abnormalities.
Manzano
Roberta Pereira de Almeida
RP
Department of Ophthalmology, Universidade de São Paulo - São Paulo (SP) - Brazil. roberta.manzano@gmail.com
Peyman
Gholam A
GA
Khan
Palwasha
P
Kivilcim
Muhamet
M
Chevez-Barrios
Patricia
P
Takahashi
Walter
W
D000818:Animals; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023421:Models, Animal; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000473:pathology; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects*; D014822:Vitreous Body / Q000187:drug effects*
D007166:Immunosuppressive Agents; D020123:Sirolimus