PMID- 11053298
OWN - NLM
STAT- MEDLINE
DCOM- 20001114
LR  - 20220310
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 41
IP  - 12
DP  - 2000 Nov
TI  - Cataractogenic lens injury prevents traumatic ganglion cell death and promotes 
      axonal regeneration both in vivo and in culture.
PG  - 3943-54
AB  - PURPOSE: To examine and quantify neuroprotective and neurite-promoting activity 
      on retinal ganglion cells (RGCs) after injury of the lens. METHODS: In adult 
      albino rats, penetrating lens injury was performed by intraocular injection. To 
      test for injury-induced neuroprotective effects in vivo, fluorescence-prelabeled 
      RGCs were axotomized by subsequent crush of the optic nerve (ON) with concomitant 
      lens injury to cause cataract. The numbers of surviving RGCs were determined in 
      retinal wholemounts and compared between the different experimental and control 
      groups. To examine axonal regeneration in vivo, the ON was cut and replaced with 
      an autologous piece of sciatic nerve (SN). Retinal ganglion cells with axons that 
      had regenerated within the SN under lens injury or control conditions were 
      retrogradely labeled with a fluorescent dye and counted on retinal wholemounts. 
      Neurite regeneration was also studied in adult retinal explants obtained either 
      after lens injury or without injury. The numbers of axons were determined after 1 
      and 2 days in culture. Putative neurotrophins (NTs) were studied within 
      immunohistochemistry and Western blot analysis. RESULTS: Cataractogenic lens 
      injury performed at the same time as ON crush resulted in highly significant 
      rescue of 746 +/- 126 RGCs/mm(2) (mean +/- SD; approximately 39% of total RGCs) 
      14 days after injury compared with controls without injury or with injection of 
      buffer into the vitreous body (30 +/- 18 RGCs/mm(2)). When lens injury was 
      performed with a delay of 3 days after ON crush, 49% of RGCs survived, whereas 
      delay of 5 days still rescued 45% of all RGCs. In the grafting paradigm virtually 
      all surviving RGCs after lens injury appeared to have regenerated an axon within 
      the SN graft (763 +/- 114 RGCs/mm(2) versus 79 +/- 17 RGCs/mm(2) in controls). 
      This rate of regeneration corresponds to approximately 40% of all RGCs. In the 
      regeneration paradigm in vitro preceding lens injury and ON crush 5 days previous 
      resulted in a maximum of regeneration of 273 +/- 39 fibers/explant after 1 day 
      and 574 +/- 38 fibers/explant after 2 days in vitro. In comparison, in control 
      retinal pieces without lens injury 28 +/- 13 fibers/explant grew out at 1 day, 
      and 97 +/- 37 fibers/explant grew out at 2 days in culture. Immunohistochemical 
      and Western blot analysis of potential NTs in the injured lens revealed no 
      expression of ciliary neurotrophic factor (CNTF), brain-derived neurotrophic 
      factor (BDNF), NT-4, nerve growth factor (NGF), and basic fibroblast growth 
      factor (bFGF). CONCLUSIONS: The findings indicate that the lens contains high 
      neuroprotective and neuritogenic activity, which is not caused by NT. Compared 
      with the data available in the literature, this neuroprotection is quantitatively 
      among the highest ever reported within the adult rat visual system.
FAU - Fischer, D
AU  - Fischer D
AD  - Department of Experimental Ophthalmology, School of Medicine, University of 
      Munster, Germany.
FAU - Pavlidis, M
AU  - Pavlidis M
FAU - Thanos, S
AU  - Thanos S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuroprotective Agents)
SB  - IM
MH  - Animals
MH  - Axons/*physiology
MH  - Axotomy
MH  - Blotting, Western
MH  - Cataract/etiology/*physiopathology
MH  - Cell Survival/*physiology
MH  - Eye Injuries, Penetrating/etiology/*physiopathology
MH  - Female
MH  - Fluorescent Antibody Technique, Indirect
MH  - Lens, Crystalline/*injuries/physiopathology
MH  - Male
MH  - Nerve Growth Factors/metabolism
MH  - Nerve Regeneration/*physiology
MH  - Neurites/physiology
MH  - Neuroprotective Agents
MH  - Optic Nerve/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Ganglion Cells/*physiology
EDAT- 2000/10/29 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/10/29 11:00
PHST- 2000/10/29 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/10/29 11:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2000 Nov;41(12):3943-54.