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L. Cadetti, H. Lorach, J. Degardin, J. A. Sahel, S. Picaud; Neuroprotection of Retinal Ganglion Cells in P23H Rats: A Way to Improve Resolution in Retinal Prosthesis or Optogenic Approach. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3700.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose :Following photoreceptor loss, restoring vision with prosthetical microchip devices or the optogenetic approach in diseases like retinitis pigmentosa or macula degeneration requires a functional inner network or at least Retinal Ganglion Cells (RGCs) connected to higher visual centres. Nonetheless, a significant loss of GCs was observed in advanced retinitis pigmentosa (Humayun, 1999) as well as in different animal models of the disease. We show that a small molecule (IDV007) pulled from a screening on pure RGCs can prevent or slow down RGCs death after the complete loss of photoreceptors.
P23H rats were administered IDV007 for 3 months because this molecule was found to prevent RGC degeneration in pure retinal RGC culture. RGCs from P23H rats and control rats were immunostained with an antibody directed against Brn3A in both slices and retinal flat mount preparations.
Rod photoreceptors degeneration is virtually complete in 6 months old homozygous P23H rats whereas almost no photoreceptors are present in 9 months old heterozygous and homozygous P23H rats. At 6 months, homozygous rats have already lost 17 % of RGC (P<0.0315, two tailed T-test), and this loss is further increased to 34% in 1 year old P23H rats (P<0.0001, two tailed T test). A similar loss was observed in heterozygous P23H rats from 9 to 12 months. When IDV007 was administered to heterozygous P23H rats, the RGC loss was slowed down. After 3 months, treated animals had 17% more GCs than untreated ones (P<0.0111, two tailed T test).
In P23H rats, the RGC number decreases during and after photoreceptor degeneration. Treatment with IDV007, which was identified for its RGC neuroprotection in vitro, partially prevented the RGC loss in P23H rats. This study suggests that improving the resolution of rehabilitating strategies (retinal prosthesis and optogenic approach) could be achieved by preventing the RGC loss in patients affected by retinitis pigmentosa.
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