title: Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses.
abstract: In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 degrees C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post-injection. Eyes were enucleated and samples were collected for RAPA concentrations and histopathology. No difference in light vs. dark RAPA concentrations was observed, suggesting a lack of RAPA phototoxicity. No evidence of ocular toxicity was noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly 7 days post-injection in eyes receiving subconjunctival RAPA, but was detected in the vitreous at 21 days post-injection. Drug could be detected in both the aqueous and vitreous humor after intravitreal injection. Further study is needed to determine the efficacy of intravitreal RAPA.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Douglas
authors.forename: N Y
authors.initials: NY
authors.lastname: Yi
authors.forename: J L
authors.initials: JL
authors.lastname: Davis
authors.forename: J H
authors.initials: JH
authors.lastname: Salmon
authors.forename: B C
authors.initials: BC
authors.lastname: Gilger
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D017484:Dermatitis, Phototoxic; D006736:Horses; D020123:Sirolimus / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014018:Tissue Distribution; D014605:Uveitis / Q000188:drug therapy / Q000662:veterinary*
chemical_list: D000900:Anti-Bacterial Agents; D020123:Sirolimus