Abstract
Abstract: :
Purpose: Use DNA microarray technology to identify the mechanisms by which the neuroprotective agents Glial-derived Neurotrphic Factor (GDNF), Ciliary Neurotrophic Factor (CNTF) and Diltiazem promote photoreceptor survival. Methods: PN15 rd1 mice were treated by subretinal injection of 330 ng of recombinant GDNF, CNTF, or by sub-cutaneous injection of diltiazem. The experiment was repeated twice. 48 hours after injection, total RNA was prepared from pools of five neural retinas of treated animal as well as from mock treated and untreated mice, labelled and hybridised to Affymetrix genechips. Results: Gene expression changes between treated and untreated rd1 mice, as well as between rd1 and congenic wild-type animals, were analysed. Changes in expression of genes of the rod phototransduction cascade is a sensor of the extent of rescue. The clustering of the data reveals common as well as divergent pathways leading to photoreceptor neuroprotection. A subset of these results has been checked by real-time RT-PCR. Conclusion: This analysis identifies signalling pathways in neuro-protection of the outer retina as well as targets for new therapeutic interventions.
Keywords: 417 gene/expression • 489 neuroprotection • 423 growth factors/growth factor receptors