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Abstract #10498 Published in IGR 6-1
Changes in retinal expression of neurotrophins and neurotrophin receptors induced by ocular hypertension
Rudzinski M; Wong TP; Saragovi HUJournal of Neurobiology 2004; 58: 341-354
Open angle glaucoma is defined as a progressive and time-dependent death of retinal ganglion cells concomitant with high intraocular pressure, leading to loss of visual field. Because neurotrophins are a family of growth factors that support neuronal survival, the authors hypothesized that quantitative and qualitative changes in neurotrophins or their receptors may take place early in ocular hypertension, preceding extensive cell death and clinical features of glaucoma. They present molecular, biochemical, and phenotypic evidence that significant neurotrophic changes occur in retina, which correlate temporally with retinal ganglion cell death. After seven days of ocular hypertension, there is a transient up-regulation of retinal NGF, while its receptor TrkA is up-regulated in a sustained fashion in retinal neurons. After 28 days of ocular hypertension, there is sustained up-regulation of retinal BDNF, but its receptor TrkB remains unchanged. Throughout, NT-3 levels remain unchanged but there is an early and sustained increase of its receptor TrkC in Muller cells but not in retinal ganglion cells. These newly synthesized glial TrkC receptors are truncated, kinase-dead isoforms. Expression of retinal p75 also increases late at day 28. Asymmetric up-regulation of neurotrophins and neurotrophin receptors may preclude efficient neurotrophic rescue of RGCs from apoptosis. A possible rationale for therapeutic intervention with Trk receptor agonists and p75 receptor antagonists is proposed.
Dr. M. Rudzinski, Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada
Classification:
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)