High doses of diltiazem may postpone blindness in people affected by retinitis pigmentosa, say researchers from the Université Louis Pasteur in Strasbourg.
Retinitis pigmentosa is an inherited, degenerative disease of photoreceptors that causes blindness. One theory of the disease is that there is an abnormal increase in cGMP concentration, which reaches levels toxic to photoreceptors and causes cell death.
According to the researchers, a good model for retinitis pigmentosa is the retinal degeneration (rd) mouse. The pattern of photoreceptor loss in rd mice is similar to that seen in humans - rod cell death is followed by cone cell degeneration. cGMP acts at the cationic channels responsible for the light-sensitive current in photoreceptors. Dr Maria Frasson and colleagues investigated the possibility of "rescuing" both rods and cones in the rd mouse using diltiazem, a calcium channel blocker known to act at cGMP-gated channels. The researchers say that rod and cone numbers decreased considerably in both treated and untreated mice, when compared with "wild-type" mice. However, rod numbers were 186 per cent higher in treated mice than in controls after 25 days of treatment, and were 248 per cent higher after 36 days. Both differences were statistically significant, they say. Differences were also statistically significant for cone cells, which were 109 and 144 per cent more numerous in the treated mice on days 25 and 36, respectively.
The authors conclude that daily diltiazem treatment (20 to 60mg/kg) partially protected both rod and cone cells from degenerating and also conserved visual function. They could not determine the mechanism by which diltiazem rescued photoreceptors but suggest that it might be through calcium channel blockade.
Initial clinical trials should be limited to patients with forms of the disease that make them most likely to benefit from this treatment, they say. However, they warn that this should be done with care as the daily dose is greater than that usually used in humans. The study is published in Nature Medicine (1999;5:1183).