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Abstract #5568 Published in IGR 2-1
Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma
Pease ME; McKinnon SJ; Quigley HA; Kerrigan-Baumrind LA; Zack DJInvestigative Ophthalmology and Visual Science 2000; 41:764-774
PURPOSE: In both animal model systems and human glaucoma, retinal ganglion cells (RGCs) die by apoptosis. To understand how RGC apoptosis is initiated in these systems, the authors studied RGC neurotrophin transport in experimental glaucoma using acute intraocular pressure (IOP) elevations in rats and chronic IOP elevation and unilateral optic nerve transections in monkeys. METHODS: Eyes were studied in masked fashion by light and electron microscopy and by immunohistochemistry with antibodies directed against the tyrosine kinase receptors (TrkA, B, and C) and against brain-derived neurotrophic factor (BDNF), as well as by autoradiography to identify retrograde axonal transport of 125I-BDNF injected into the superior colliculus. RESULTS: With acute glaucoma in the rat, RGC axons became abnormally dilated, accumulating vesicles presumed to be moving in axonal transport at the optic nerve head. Label for TrkB, but not TrkA, was relatively increased at and behind the optic nerve head with IOP elevation. Abnormal, focal labelling for TrkB and BDNF was identified in axons of monkey optic nerve heads with chronic glaucoma. With acute IOP elevation in rats, radiolabelled BDNF arrived at cells in the RGC layer at less than half the level of control eyes. CONCLUSIONS: Interruption of BDNF retrograde transport and accumulation of TrkB at the optic nerve head in acute and chronic glaucoma models suggest a role for neurotrophin deprivation in the pathogenesis of RGC death in glaucoma.
Dr. M.E. Pease, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
5 Experimental glaucoma; animal models
