Intravitreal injections of neurotrophic factors and forskolin enhance survival and axonal regeneration of axotomized β ganglion cells in cat retina

Some retinal ganglion cells in adult cats survive axotomy for two months and regenerate their axons when a peripheral nerve is transplanted to the transected optic nerve. However, regenerated retinal ganglion cells were fewer than 4% of the total retinal ganglion cell population in the intact retina...

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Bibliographic Details
Published in:Neuroscience 2003-01, Vol.116 (3), p.733-742
Main Authors: Watanabe, M, Tokita, Y, Kato, M, Fukuda, Y
Format: Article
Language:English
Subjects:
Animals
Axons - drug effects
Axons - physiology
Axotomy
BDNF
Biological and medical sciences
cAMP
Cats
Cell Count - methods
Cell Survival - drug effects
Cell Survival - physiology
CNTF
Colforsin - pharmacology
Drug Combinations
Eye and associated structures. Visual pathways and centers. Vision
Fundamental and applied biological sciences. Psychology
Nerve Growth Factors - pharmacology
Nerve Regeneration - drug effects
Nerve Regeneration - physiology
Retina - drug effects
Retina - physiology
retinal ganglion cell
Retinal Ganglion Cells - drug effects
Retinal Ganglion Cells - physiology
survival after axotomy
transplantation
Vertebrates: nervous system and sense organs
Vitreous Body - drug effects
Vitreous Body - physiology
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Summary:Some retinal ganglion cells in adult cats survive axotomy for two months and regenerate their axons when a peripheral nerve is transplanted to the transected optic nerve. However, regenerated retinal ganglion cells were fewer than 4% of the total retinal ganglion cell population in the intact retina. The present study examined the effects of intravitreal injections of neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, basic fibroblast growth factor, glial cell-derived neurotrophic factor, neurotrophin 4), first on the survival of axotomized cat retinal ganglion cells within 2 weeks, and then on axonal regeneration of the retinal ganglion cells for 2 months after peripheral nerve transplantation. We tested first enhancement of the survival by one of the factors, and then one or two of them supplemented with forskolin, which increases intracellular cAMP. Single injections of 0.5 μg or 1 μg brain-derived neurotrophic factor, 1 μg ciliary neurotrophic factor, or 1 μg glial cell-derived neurotrophic factor significantly increased total numbers of surviving retinal ganglion cells; 1.6–1.8 times those in control retinas. Identification of retinal ganglion cell types with Lucifer Yellow injections revealed that the increase of surviving β cells was most conspicuous: 2.5-fold (brain-derived neurotrophic factor) to 3.6-fold (ciliary neurotrophic factor). A combined injection of 1 μg brain-derived neurotrophic factor, 1 μg ciliary neurotrophic factor, and 0.1 mg forskolin resulted in a 4.7-fold increase of surviving β cells, i.e. 50% survival on day 14. On the axonal regeneration by peripheral nerve transplantation, a combined injection of brain-derived neurotrophic factor, ciliary neurotrophic factor, and forskolin resulted in a 3.4-fold increase of β cells with regenerated axons. The increase of regenerated β cells was mainly due to the enhancing effect of neurotrophic factors on their survival, and possibly to a change of retinal ganglion cell properties by cAMP to facilitate their axonal regeneration.
ISSN:0306-4522
1873-7544
DOI:10.1016/S0306-4522(02)00562-6