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Effects of epidermal growth factor and erythropoietin on Müller glial activation and phenotypic plasticity in the adult mammalian retina
Author(s) -
Nickerson P.E.B.,
McLeod M.C.,
Myers T.,
Clarke D.B.
Publication year - 2011
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22629
Subject(s) - retina , glial fibrillary acidic protein , biology , retinal , microbiology and biotechnology , muller glia , epidermal growth factor , erythropoietin , nestin , gliosis , growth factor , neuroglia , progenitor cell , neural stem cell , neuroscience , stem cell , endocrinology , immunology , central nervous system , cell culture , immunohistochemistry , biochemistry , genetics , receptor
Retinal Müller glia have received considerable attention with regard to their potential to function as quiescent retinal precursors. Various activation strategies induce characteristic features of retinal progenitor cells in Müller glia; however, these are often accompanied by hallmark features of reactive gliosis. We investigated the effects of an intravitreal injection of epidermal growth factor (EGF), a known mitogen, and erythropoietin (EPO) on activation and expression of developmental phenotypes within the adult retina. Using thymidine‐analogue labeling as well as immunocytochemical and confocal analyses, we assayed the responses of retinal cells exposed to intravitreal administration of either EGF or EPO. We report that adult Müller glia incorporate bromodeoxyuridine (BrdU) and undergo a process of nuclear translocation to ectopic retinal layers following exposure to EGF. These cells survive within the retina for at least 23 days and express the developmental markers Pax6 and Chx10 as well as nestin and glial fibrillary acidic protein. Furthermore, we demonstrate that cotreatment with EGF and EPO suppresses aspects of EGF‐induced glial reactivity, alters the retinal distribution of BrdU‐positive nuclei, and serves to regulate the expression of developmental phenotypes seen in these cells. These data further our understanding of Müller cell responsiveness to intravitral, combinatorial growth factor treatments. © 2011 Wiley‐Liss, Inc.