title: Müller glia express rhodopsin in a mouse model of inherited retinal degeneration.
abstract: The Müller glial cells exhibit stem cell properties and express neuronal markers following experimentally induced retinal injury. However, it is not known whether Müller glia respond similarly to degenerative neuronal loss caused by genetic mutation. Here, we asked whether Müller cells dedifferentiate and express neuronal proteins in rd1 mouse, a naturally occurring mutant model of inherited retinal degeneration. Using immunohistochemistry and Western blotting, we studied expression patterns of glial fibrillary acidic protein (GFAP), nestin, rhodopsin, protein kinase C alpha (PKCα), β-III-tubulin and recoverin in Müller glia. Reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to detect any rhodopsin mRNA in the rd1 mouse retina. We found that Müller cell processes in rd1 mouse hypertrophied and overexpressed GFAP as early as postnatal day (P)-14, features that were maintained throughout development and in the adult stage. Furthermore, Müller cells continued to express nestin, a progenitor cell marker, up to 6 months of age, raising the possibility that they remain undifferentiated for several months in rd1 mouse. We did not find nestin expression in Müller cells in 1-year-old rd1 mouse. Interestingly, Müller cell processes in rd1 mouse also expressed rhodopsin, a rod-specific protein. The rhodopsin expression in Müller cells was evident at P-21, and remained so up to at least 1 year of age. The expression of rhodopsin by Müller cells was further supported by our finding of the rhodopsin transcript in the 9-month-old rd1 mouse retina. We did not find the expression of PKCα, β-III-tubulin or recoverin in Müller cells in adult rd1 mouse. These results suggested that Müller cells in rd1 mouse express proteins specific to retinal neurons that are the primary targets of the mutation in this mouse. Although the functional significance of rhodopsin expression by Müller cells is unclear, these results have implications for novel therapeutic strategies for retinal degeneration.
authors.affiliation: National Brain Research Centre, Manesar (Gurgaon) 122051, India.
authors.forename: M
authors.initials: M
authors.lastname: Goel
authors.forename: N K
authors.initials: NK
authors.lastname: Dhingra
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012243:Rhodopsin; D011493:Protein Kinase C; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6