Ocular Distribution After Topical Instillation and Potential Neuroprotective Effect After Intravitreal Injection of the Calcium Channel Blocker Iganipidine

Abstract

Purpose: To investigate the effects of iganidipine, a new calcium antagonist on glutamate agonist–induced retinal damage. Methods: Iganidipine was injected with N-methyl-d-aspartate (NMDA) or kainic acid (KA) into the rat vitreous, and the retina was histologically examined. After co-injection with KA, the number of DiI-labeled retinal ganglion cells was also counted. Rabbits received unilateral instillation of 0.03% iganidipine twice daily for 14 days, and the iganidipine level in the posterior retina-choroid was determined by liquid chromatography/mass spectrometry. Results: Coadministration of iganidipine had no significant effect on NMDA-induced thinning of the inner plexiform layer but partly suppressed KA-induced thinning at final intravitreous concentrations of 10^{− 8} M or higher, which was confirmed by counting the ganglion cell number. The iganidipine level in the posterior retina-choroid was approximately 6.2 × 10^{− 7} M in the instilled eye, which was higher than on the contralateral side by 5.2 × 10^{− 7} M (p = 0.035). Conclusions: Iganidipine suppressed KA-induced retinal damage in rats. This suppression was achieved with a lower concentration than that resulting from unilateral instillations of iganidipine in the ipsilateral posterior retina-choroid in rabbits.

KEYWORDS:

• glutamate agonist-induced retinal damage
• iganidipine
• ocular penetration
• topical instillation