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Nicolas G. Froger, Julie Dégardin, Dorothée Pain, Elisabeth Dubus, Valérie Forster, Manuel Simonutti, Alexis-Pierre Bemelmans, José-Alain Sahel, Serge Picaud; A Neuroprotective Molecule For Retinal Ganglion Cells In Different Cellular And Animal Models Of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1874.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma, the second cause of blindness worldwide, is a retinopathy characterized by retinal ganglion cells (RGC) degeneration. Current treatments aim at reducing the increase in intra-ocular pressure (IOP) occurred in most glaucoma, whereas no drug targeting neuroprotection is available. To isolate, neuroprotective molecules, we have screened a library on pure adult rat retinal ganglion cells. Then, one protective molecule, IDV007, was validated on NMDA-treated retinal explants, DBA/2J mice and rats with episcleral vein occlusion.
Pure RGC from adult rat retinas were cultured for 6 DIV and survival was assessed by calcein-positive RGC counting. NMDA-treated retinal explants were cultured for 4 DIV and Brn-3a-positive RGC density was evaluated on whole-mounts by automatic counting. 8-month old DBA2/J mice and rats with episcleral vein occlusion were treated orally for 4 months and 3 months, respectively. The increase in intraocular pressure was measured every month, electroretinograms were monitored in rats and the RGC density was quantified following Brn-3a-immunolabelling on dorso-ventral retinal cryosections.
IDV007 treatment stimulated the survival (+69%) of cultured adult rat RGCs and significantly rescued the RGC loss (+22%) in NMDA-treated retinal explants. IDV007 oral treatment in both cauterized rats or in DBA/2J mice did not modify the elevated IOP. Interestingly, the treatment led to significant recovery of RGC density (+16%) in DBA/2J mice. In rats with episcleral vein occlusion, the treatment prevented the decrease in the photopic ERG and the loss of RGC density (87%).
These data indicated that IDV007 treatments can stimulate RGC survival in different pathological conditions: deprived in vitro conditions, NMDA-induced excitotoxicity and in vivo increased intraocular pressure. Future studies are investigating further this new mechanism of RGC neuroprotection.
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