PMID- 10711692
OWN - NLM
STAT- MEDLINE
DCOM- 20000315
LR  - 20220321
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 41
IP  - 3
DP  - 2000 Mar
TI  - Obstructed axonal transport of BDNF and its receptor TrkB in experimental 
      glaucoma.
PG  - 764-74
AB  - 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.
FAU - Pease, M E
AU  - Pease ME
AD  - Department of Ophthalmology, Johns Hopkins University School of Medicine, 
      Baltimore, Maryland, USA.
FAU - McKinnon, S J
AU  - McKinnon SJ
FAU - Quigley, H A
AU  - Quigley HA
FAU - Kerrigan-Baumrind, L A
AU  - Kerrigan-Baumrind LA
FAU - Zack, D J
AU  - Zack DJ
LA  - eng
GR  - EY 00361/EY/NEI NIH HHS/United States
GR  - EY 01765/EY/NEI NIH HHS/United States
GR  - EY 02120/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Autoradiography
MH  - *Axonal Transport
MH  - Axons/metabolism/pathology/ultrastructure
MH  - Axotomy
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Chronic Disease
MH  - Disease Models, Animal
MH  - Glaucoma/*metabolism/pathology
MH  - Immunoenzyme Techniques
MH  - Intraocular Pressure
MH  - Macaca fascicularis
MH  - Male
MH  - Optic Disk/*metabolism/pathology/ultrastructure
MH  - Rats
MH  - Rats, Inbred BN
MH  - Receptor, trkB/*metabolism
MH  - Retinal Ganglion Cells/*metabolism/pathology/ultrastructure
EDAT- 2000/03/11 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/03/11 09:00
PHST- 2000/03/11 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/03/11 09:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2000 Mar;41(3):764-74.