Basic fibroblast growth factor-induced protection from light damage in the mouse retina in vivo |
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Authors: | O'Driscoll Carolyn O'Connor Jeremy O'Brien Colm J Cotter Thomas G |
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Affiliation: | Cell Development and Disease Laboratory, Biochemistry Department, Bioscience Research Institute, University College Cork, Cork, Ireland; Institute of Ophthalmology, Mater Misericordiae Hospital and Conway Institute, University College Dublin, Dublin, Ireland |
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Abstract: | Basic fibroblast growth factor (bFGF) has proven neuroprotective efficacy in the rodent retina against a diverse array of injurious stimuli. However, there is no consensus to date as to the molecular mechanisms underlying this neuroprotection. The study presented herein demonstrates increased expression of endogenous bFGF in the albino mouse retina in response to acute exposure to sublethal levels of light stress. The increased expression correlates with significant photoreceptor protection from light damage. The neuroprotection is likely to be mediated by bFGF as we demonstrate that a shorter exposure to bright light stress that does not up-regulate bFGF fails to protect photoreceptors from light damage. Furthermore, intravitreal bFGF injection into the retina of mice 3 h prior to light damage affords almost complete photoreceptor protection from light-induced degeneration. In addition, injected bFGF induces the activation of protein kinase B and extracellular signal-regulated kinase 1/2 signalling which correlate directly with the pathways we find to be activated in response to light stress and up-regulated bFGF. Moreover, we demonstrate that both bright light pre-conditioning and intravitreal bFGF injection result in dramatic increases in levels of inactive glycogen synthase kinase 3β and cyclic AMP response element binding protein phosphorylation indicating a potential mechanism by which bFGF promotes survival of photoreceptors in vivo . |
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Keywords: | basic fibroblast growth factor growth factor light damage neuroprotection photoreceptor pre-conditioning |
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