Editors Selection IGR 11-4

Basic Research: RGC death and lomerizine

Makoto Araie

Comment by Makoto Araie on:

24832 Secondary retinal ganglion cell death and the neuroprotective effects of the calcium channel blocker lomerizine, Fitzgerald M; Payne SC; Bartlett CA et al., Investigative Ophthalmology and Visual Science, 2009; 50: 5456-5462

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Japan Successful IOP reduction eliminates mechanical insult that leads to primary RGC death. Secondary retinal ganglion cell (RGC) death also has clinical implications in glaucoma, especially in cases of late stage of the disease where only a part of RGCs are still surviving, and it is of clinical importance to protect these RGCs. Using partial transaction of the optic nerve (ON) as an experimental model, Fitzgerald et al. (1636) studied the mechanism of the secondary RGC death and evaluated the effect of a calcium channel blocker (CCB), lomerizine. An interesting finding obtained by the authors is that the most of the secondary RGC death was due to necrotic, but not apoptotic processes. Further, lomerizine was found to reduce the secondary necrotic RGC death by about 70%. Intracelullar calciumdependent signalling pathways are involved in many of the cellular functions including necrotic and/or apoptotic cell death. Because of minimal systemic circulatory effects, lomerizine is a CCB that may be considered for prescription to patients with ocular diseases by an ophthalmologist. We have also studied potential of lomerizine as an ophthalmologic CCB (Shimazawa, et al. Exp Eye Res 1999; Tamaki, et al. IOVS 2003; Yamada, et al. Brain Res 2006). Since the effects of lomerizine on the optic nerve head and/or retinal circulation in experimental animals and humans were significant, but relatively small, lomerizine's potential as an ophthalmic CCB was thought to be dependent not on its ocular vasodilatory action, but its direct action on L-type calcium channels of neurons (Hara, et al. Neurosci Ther 1995; Yamada, et al. Brain Res 2006). The authors' current results have not only demonstrated the potential of lomerizine in the treatment of the secondary RGC death, but also suggested that pharmacological agents inhibiting necrotic signal pathways, including calpain inhibitors, have potential to be used to ameliorate the secondary RGC death in glaucoma. The authors also found that lomerizine was effective in alleviating the secondary apoptotic RGC death, which may also suggest potential of lomerizine in alleviating primary apoptotic RGC death.

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