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Dietmar Fischer, Mitrofanis Pavlidis, Solon Thanos; Cataractogenic Lens Injury Prevents Traumatic Ganglion Cell Death and Promotes Axonal Regeneration Both In Vivo and in Culture. Invest. Ophthalmol. Vis. Sci. 2000;41(12):3943-3954.
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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/mm2 (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/mm2). 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/mm2 versus
79 ± 17 RGCs/mm2 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
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