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Fabio Gasparin, Renata G. Aguiar, Gabriela L. Ioshimoto, Armando S. Cunha, Jr., Maira F. Carneiro, Andre M. Liber, Dora F. Ventura, Francisco M. Damico; Electroretinographic And Morphologic Findings After Mycophenolic Acid Intravitreal Injection In Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1691.
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Mycophenolate mofetil (MMF) is a potent immunomodulatory drug used in the treatment of patients with autoimmune uveitis. However, gastrointestinal side effects occur in up to 20% of patients and are the main reason for discontinuation. Mycophenolic acid (MPA) is the active form of MMF. We injected 5 doses of MPA in the rabbit vitreous and evaluated the retinal function by electroretinography (ERG) and morphological effects by light microscopy.
Aqueous suspension of MPA (Roche, Palo Alto, CA) was injected in the vitreous of 24 New Zealand rabbits (5, 50, 200, 1000, and 10000µg/0.1ml). As control, contralateral eye of each rabbit was injected with aqueous vehicle. ERG was recorded before injection, and at days 7, 14, and 30. Slit-lamp and fundus exams were performed and signs of infection and inflammation were recorded. Animals were sacrificed at day 30 and retinas were analyzed by light microscopy.
Eyes injected with MPA did not present clinical signs of intraocular inflammation with any of the injected doses. ERG records showed that eyes injected with 5 to 1000µg did not show either scotopic or photopic a- and b-wave changes, as well as eyes injected with vehicle. Eyes injected with 10000µg presented scotopic a-wave amplitude reduction by 21% (P=0.03) and b-wave implicit time reduction by 11% (P=0.08) 30 days after injection, suggesting bipolar and Müller cells damage. Light microscopy showed inner nuclear layer thinning in eyes injected with 1000 and 10000µg, also suggesting same cell types damage.
Intravitreal injection of 1000 and 10000µg MPA produce functional and morphologic changes in rabbit retina while lower doses seem to be safe. These data suggest that intravitreal injection of MPA is a potential treatment for autoimmune uveitis. However more studies should be carried before it is used in clinical practice.
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