Müller cells can be activated and included in different functions under many kinds of pathological conditions, however, the status of Müller cells in retinitis pigmentosa are still unknown. Using immunohistochemisty, Western blots and co-culture, we found that Müller cells RCS rats, a classic model of RP, could be activated during the progression of retinal degeneration. After being activated at early stage, Müller cells began to proliferate and hypertrophy, while at later stages, they formed a local ‘glial seal’ in the subretinal space. As markers of Müller cells activation, the expression of GFAP and ERK increased significantly with progression of retinal degeneration. Co-cultures of normal rat Müller cells and mixed RCS rat retinal cells show that Müller cells significantly increase GFAP and ERK in response to diffusable factors from the degenerting retina, which implies that Müller cells activation is a secondary response to retinal degeneration.
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The authors thank Dr. T. Fitz Gibon for comments on earlier drafts of the paper; Yu Xiao Zeng, Dong Ning Liu, Li Feng Chen, Yan Hua Wang for excellent technical support. This work was supported by the National Basic Research Program of China (Grant No. 2007CB512203), and the funds from a Nature Science Foundation of China (Grant No. 30772371).
Bringmann A, Reichenbach A, Wiedemann P (2004) Pathomechanisms of cystoid macular edema. Ophthalm Res 36:241–249CrossRefGoogle Scholar
Clyde G (2005) The role of Müller cells in fibrocontractive retinal disorders. Prog Retin Eye Res 24:75–86CrossRefGoogle Scholar
Fletcher EL, Phipps JA, Wilkinson-Berka JL (2005) Dysfunction of retinal neurons and glia during diabetes. Clin Exp Optom 88:132–145CrossRefPubMedGoogle Scholar
Francke M, Faude F, Pannicke T et al (2001) Electrophysiology of rabbit Müller (glial) cells in experimental retinal detachment and PVR. Invest Ophthalmol Vis Sci 42:1072–1079PubMedGoogle Scholar
Gulgun T, Balwantray CC, Raymond PL et al (2003) Immunohistochemical assessment of the glial mitogen-activated protein kinase activation in glaucoma. Invest Ophthalmol Vis Sci 44:3025–3033Google Scholar
Hicks D, Courtois Y (1990) The growth and behaviour of rat retinal Müller cells in vitro. 1. An improved method for isolation and culture. Exp Eye Res 51:119–129CrossRefPubMedGoogle Scholar
Lund RD, Kwan ASL, Keegan DJ (2001) Cell transplantation as a treatment for retinal disease. Prog Retin Eye Res 20(4):415–449CrossRefPubMedGoogle Scholar
Masumi T, Akira T, Akitoshi Y et al (2002) Extracellular signal-regulated kinase activation predominantly in Müller cells of retina with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 43:907–911Google Scholar
Newman EA (1996) Acid efflux from retinal glial cells generated by sodium bicarbonate cotransport. J Neurosci 16:159–168PubMedGoogle Scholar
Newman EA, Zahs KR (1998) Modulation of neuronal activity by glial cells in the retina. J Neurosci 18:4022–4028PubMedGoogle Scholar
Ortrud U, Susann U, Michael W et al (2003) Upregulation of purinergic P2Y receptor-mediated calcium responses in glial cells during experimental detachment of the rabbit retina. Neurosci Lett 338:131–134CrossRefGoogle Scholar
Reichenbach A, Stolzenburg J-U, Wolburg H et al (1995) Effects of enhanced extracellular ammonia concentration on cultured mammalian retinal glial (Müller) cells. Glia 13:195–208CrossRefPubMedGoogle Scholar
Robert EM, Bryan WJ, Carl BW et al (2003) Neural remodeling in retinal degeneration. Prog Retin Eye Res 22:607–655CrossRefGoogle Scholar
Scott FG, Geoffrey PL, Steven KF (2001) FGFR1, signaling and AP-1 expression after retinal detachment: reactive Müller and RPE cells. Invest Ophthalmol Vis Sci 42:1363–1369Google Scholar
Steven KF, Geoffrey PL (2003) Müller cell and neuronal remodeling in retinal detachment and reattachment and their potential consequences for visual recovery: a review and reconsideration of recent data. Vis Res 43:887–897CrossRefGoogle Scholar
Stevens ER, Esguerra M, Kim PM et al (2003) D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors. Proc Natl Acad Sci USA 100:6789–6794CrossRefPubMedGoogle Scholar
Stier H, Schlosshauer B (1998) Different cell surface areas of polarized radial glia having opposite effects on axonal outgrowth. Eur J Neurosci 10:1000–1010CrossRefPubMedGoogle Scholar
Sullivan R, Penfold P, Pow DV (2003) Neuronal migration and glial remodeling in degenerating retinas of aged rats and in nonneovascular AMD. Invest Ophthalmol Vis Sci 44:856–865CrossRefPubMedGoogle Scholar
Vijay S (2007) Focus on molecules: glial fibrillary acidic protein (GFAP). Exp Eye Res 84:381–382CrossRefGoogle Scholar
Willbold E, Berger J, Reinicke M et al (1997) On the role of Müller glia cells in histogenesis: only retinal spheroids, but not tectal, telencephalic and cerebellar spheroids develop histotypical patterns. J Hirnforsch 38:383–396PubMedGoogle Scholar
Xue LP, Lu J, Cao Q et al (2006) Müller glial cells express nestin coupled with gilal fibrillary acidic protein in experimentally induced glaucoma in the rat retina. Neuroscience 139:723–732CrossRefPubMedGoogle Scholar
Yang JY, Zong CS, Xia W et al (2008) ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation. Nat Cell Biol 10(2):138–148CrossRefPubMedGoogle Scholar