Different aspects of gliosis in retinal Müller glia can beinduced by CNTF, insulin, and FGF2 in the absence of damage

[摘要] Purpose: In response to acute damage, Müller glia in the retinahave been shown to dramatically alter their expression of filamentousproteins. Since damaged retinal cells are known to produce growthfactors such as insulin-like growth factor (IGF), ciliary neurotrophicfactor (CNTF) and fibroblast growth factor (FGF), the altered expressionof filaments in Müller glia in response to retinal damage may beinduced by some of these factors. The purpose of this study was to assaywhether growth factors influence the expression of filamentous proteinsin Müller glia in the intact retinas of postnatal chickens.Methods: We assayed for changes in expression levels of IGF-I,IGF-II, CNTF, FGF1, and FGF2 in N-methyl-D-aspartate(NMDA) damagedretinas by using quantitative PCR. In undamaged retinas, we assayedwhether intraocular injections of insulin, CNTF, or FGF2 influencedglial expression of glial fibrillary acidic protein (GFAP),neurofilament, RA4, vimentin and β3 tubulin by usingimmunocytochemistry on frozen sections.Results: We demonstrated that levels of mRNA for IGF-II, FGF1, FGF2,and CNTF were increased in the postnatal chicken retina in response toneurotoxic damage. This was coincident with increased glial expressionof GFAP and filamentous neuronal proteins. The combination of insulinand FGF2 caused postmitotic Müller glia to transiently increase theirexpression of vimentin and putative neuron specific filamentous proteinssuch as neurofilament, β3 tubulin and RA4. By comparison, insulinor FGF2 alone had minor effects on glial expression of cytoskeletalproteins. Although neurofilament expression was not induced by CNTF,this growth factor stimulated Müller glia to express GFAP.Conclusions: We conclude that the phenotype of postmitotic Müllerglia is plastic and can be regulated by retinal damage, and these damageinduced changes in phenotype can be induced by exogenous growth factorsin the absence of damage.

[学科分类] 生物化学/生物物理