PMID- 9162875
OWN - NLM
STAT- MEDLINE
DCOM- 19970527
LR  - 20190920
IS  - 0161-6412 (Print)
IS  - 0161-6412 (Linking)
VI  - 18
IP  - 2
DP  - 1996 Apr
TI  - Tumor necrosis factor-alpha (TNF-alpha)-induced optic neuropathy in rabbits.
PG  - 176-84
AB  - Both in vitro and in vivo studies have implicated a role for tumor necrosis 
      factor-alpha (TNF alpha) in various demyelinating diseases, including HIV-related 
      encephalopathy. To investigate whether intravitreal TNF alpha can induce optic 
      nerve axonal damage in a rabbit eye model, fifteen rabbit eyes were initially 
      injected with TNF alpha (final concentrations: 2U, 20U, and 200U respectively) 
      and studied at varying time intervals for up to 24 weeks post-injection, using 
      light and electron microscopy. Control optic nerves (no injection or diluent 
      injection only) had normal myelinated axons and glia; the myelinated regions, 
      neural retina, retinal glia and vasculature of control retinas were normal. In 
      TNF alpha-exposed optic nerves, intact, degenerating and demyelinated axons were 
      interspersed. Astrogliosis was present, particularly from 8 weeks p.i. and was 
      noted up to 24 weeks. Oligodendrocytes were not severely affected in TNF 
      alpha-exposed optic nerves, and activated macrophages or microglia were not 
      obvious. Axonal degeneration was visible among the more superficial myelinated 
      fibers in TNF alpha-exposed retinas however the neural retina glia were 
      unaffected. These observations suggest that the axonal degeneration induced in 
      TNF alpha-exposed rabbit optic nerves over a 24 week period was most likely 
      related to direct effects of TNF alpha on optic nerve axons, and not primarily 
      due to anterograde degeneration from retinal lesions. In-so-far as neurological 
      pathology in general, and optic nerve degeneration in particular, has been 
      described in AIDS, and TNF alpha levels may be elevated in this disease, it is of 
      great clinical significance that TNF alpha has the capacity to mediate neuronal 
      or axonal injury. If so, strategies to block or inhibit TNF alpha can be pursued 
      for treatment for the neurological symptoms of AIDS.
FAU - Madigan, M C
AU  - Madigan MC
AD  - Department of Clinical Ophthalmology, University of Sydney, Australia.
FAU - Sadun, A A
AU  - Sadun AA
FAU - Rao, N S
AU  - Rao NS
FAU - Dugel, P U
AU  - Dugel PU
FAU - Tenhula, W N
AU  - Tenhula WN
FAU - Gill, P S
AU  - Gill PS
LA  - eng
GR  - R01-EY-08145/EY/NEI NIH HHS/United States
GR  - R01-EY-09510/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  - England
TA  - Neurol Res
JT  - Neurological research
JID - 7905298
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Astrocytes/pathology
MH  - Axons/pathology
MH  - Gliosis/pathology
MH  - Male
MH  - Nerve Degeneration
MH  - Oligodendroglia/pathology
MH  - Optic Nerve/pathology
MH  - Optic Nerve Diseases/*chemically induced/pathology
MH  - Rabbits
MH  - Retina/pathology
MH  - *Tumor Necrosis Factor-alpha
EDAT- 1996/04/01 00:00
MHDA- 1996/04/01 00:01
CRDT- 1996/04/01 00:00
PHST- 1996/04/01 00:00 [pubmed]
PHST- 1996/04/01 00:01 [medline]
PHST- 1996/04/01 00:00 [entrez]
AID - 10.1080/01616412.1996.11740399 [doi]
PST - ppublish
SO  - Neurol Res. 1996 Apr;18(2):176-84. doi: 10.1080/01616412.1996.11740399.