PURPOSE: In both animal model system and in 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 labeling for TrkB and BDNF was identified in axons of monkey optic nerve heads with chronic glaucoma. With acute IOP elevation in rats, radiolabeled 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.
PURPOSE: In both animal model system and in humanglaucoma, 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 labeling for TrkB and BDNF was identified in axons of monkey optic nerve heads with chronic glaucoma. With acute IOP elevation in rats, radiolabeled 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.
Authors: John Danias; Fran Shen; Manolis Kavalarakis; Bin Chen; David Goldblum; Kevin Lee; Maria-Florencia Zamora; YanLing Su; Scott E Brodie; Steven M Podos; Thom Mittag Journal: Exp Eye Res Date: 2005-08-16 Impact factor: 3.467
Authors: Axel Petzold; Anselm Junemann; Konrad Rejdak; Tomasz Zarnowski; Sebastian Thaler; Pawel Grieb; Friedrich E Kruse; Eberhart Zrenner; Robert Rejdak Journal: J Neural Transm (Vienna) Date: 2009-09-22 Impact factor: 3.575
Authors: Lidawani Lambuk; Azliana Jusnida Ahmad Jafri; Natasha Najwa Nor Arfuzir; Igor Iezhitsa; Renu Agarwal; Khairul Nizam Bin Rozali; Puneet Agarwal; Nor Salmah Bakar; Methil Kannan Kutty; Ahmad Pauzi Md Yusof; Anna Krasilnikova; Alexander Spasov; Alexander Ozerov; Nafeeza Mohd Ismail Journal: Neurotox Res Date: 2016-08-27 Impact factor: 3.911