PURPOSE: In response to acute damage, Muller glia in the retina have been shown to dramatically alter their expression of filamentous proteins. Since damaged retinal cells are known to produce growth factors such as insulin-like growth factor (IGF), ciliary neurotrophic factor (CNTF) and fibroblast growth factor (FGF), the altered expression of filaments in Muller glia in response to retinal damage may be induced by some of these factors. The purpose of this study was to assay whether growth factors influence the expression of filamentous proteins in Muller 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) damaged retinas by using quantitative PCR. In undamaged retinas, we assayed whether intraocular injections of insulin, CNTF, or FGF2 influenced glial expression of glial fibrillary acidic protein (GFAP), neurofilament, RA4, vimentin and beta3 tubulin by using immunocytochemistry 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 to neurotoxic damage. This was coincident with increased glial expression of GFAP and filamentous neuronal proteins. The combination of insulin and FGF2 caused postmitotic Muller glia to transiently increase their expression of vimentin and putative neuron specific filamentous proteins such as neurofilament, beta3 tubulin and RA4. By comparison, insulin or FGF2 alone had minor effects on glial expression of cytoskeletal proteins. Although neurofilament expression was not induced by CNTF, this growth factor stimulated Muller glia to express GFAP. CONCLUSIONS: We conclude that the phenotype of postmitotic Muller glia is plastic and can be regulated by retinal damage, and these damage induced changes in phenotype can be induced by exogenous growth factors in the absence of damage.
PURPOSE: In response to acute damage, Muller glia in the retina have been shown to dramatically alter their expression of filamentous proteins. Since damaged retinal cells are known to produce growth factors such as insulin-like growth factor (IGF), ciliary neurotrophic factor (CNTF) and fibroblast growth factor (FGF), the altered expression of filaments in Muller glia in response to retinal damage may be induced by some of these factors. The purpose of this study was to assay whether growth factors influence the expression of filamentous proteins in Muller 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) damaged retinas by using quantitative PCR. In undamaged retinas, we assayed whether intraocular injections of insulin, CNTF, or FGF2 influenced glial expression of glial fibrillary acidic protein (GFAP), neurofilament, RA4, vimentin and beta3 tubulin by using immunocytochemistry 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 to neurotoxic damage. This was coincident with increased glial expression of GFAP and filamentous neuronal proteins. The combination of insulin and FGF2 caused postmitotic Muller glia to transiently increase their expression of vimentin and putative neuron specific filamentous proteins such as neurofilament, beta3 tubulin and RA4. By comparison, insulin or FGF2 alone had minor effects on glial expression of cytoskeletal proteins. Although neurofilament expression was not induced by CNTF, this growth factor stimulated Muller glia to express GFAP. CONCLUSIONS: We conclude that the phenotype of postmitotic Muller glia is plastic and can be regulated by retinal damage, and these damage induced changes in phenotype can be induced by exogenous growth factors in the absence of damage.
Authors: Christopher P Zelinka; Leo Volkov; Zachary A Goodman; Levi Todd; Isabella Palazzo; William A Bishop; Andy J Fischer Journal: Development Date: 2016-04-11 Impact factor: 6.868
Authors: Kimberly A Toops; Cynthia Berlinicke; Donald J Zack; Robert W Nickells Journal: Invest Ophthalmol Vis Sci Date: 2012-04-24 Impact factor: 4.799
Authors: Corinne R Wittmer; Thomas Claudepierre; Michael Reber; Peter Wiedemann; Jonathan A Garlick; David Kaplan; Christophe Egles Journal: Adv Funct Mater Date: 2011-11-16 Impact factor: 18.808