Electrophysiological study of the retinal effects of intravitreal injection of mycophenolic acid in rabbits

Abstract

 

Purpose

 

Uveitis is an intraocular inflammation and a leading cause of blindness in the world. Mycophenolate mofetil (MMF) is a potent immunosuppressant drug administered orally that has been successfully used in the treatment of patients with autoimmune uveitis. However, treatment has to be discontinued in up to 20% of patients due to systemic side effects. MMF is a prodrug that is converted in the liver to mycophenolic acid (MPA), the active drug. The aim of this study is to determine the electrophysiological retinal effects of MPA after intravitreal injection of different doses in rabbits

 

Methods

 

Aqueous suspension of MPA (Roche, Palo Alto, CA) was injected in the vitreous of 30 albino New Zealand rabbits (0.01, 0.1, and 1 mg - 10 animals for each dose). Polysorbate 80 (vehicle) was injected in the left eye as control. The electroretinogram (ERG) (Roland Consult, Germany) was recorded under a modified ISCEV protocol with dark adapted animals. ERGs performed before and after intravitreal injections (days 3, 7, 14, 21 and 30) were compared. The statistical comparisons were made by ANOVA and the post hoc test used was the Tukey test

 

Results

 

Scotopic ERG a- and b-wave amplitudes and implicit times from eyes with MPA did not differ statistically from the control eyes for any of the 3 doses tested in any of the 5 flash intensities (P>0.05). Table 1 shows ERG values for MPA 1 mg. Vmax, K and n parameters obtained from the response vs. flash intensity curve using the Naka-Rushton equation showed no difference between experimental and control eyes (P>0.05, Table 2)

 

Conclusions

 

Intravitreal injection of MPA 0.01 to 1 mg did not impair the retinal function in rabbit eyes, suggesting that these doses may be non-toxic to the retina. Intravitreal injection of MPA may be an adjunctive therapy for the treatment of corticosteroid-resistant autoimmune uveitis patients or in patients with MMF systemic side effects