title: Preferential regeneration of photoreceptor from Müller glia after retinal degeneration in adult rat.
abstract: To determine whether photoreceptor degeneration can stimulate Müller glia to transdifferentiate into neurons in adult mammalian retina, N-methyl-N-nitrosourea (MNU) was injected to induce complete loss of photoreceptors. Following MNU administration, Müller glia underwent reactive gliosis characterized by up-regulation of glial fibrillar acidic protein and nestin, and initiated proliferation through the cyclin D1 and D3 related pathways. Some Müller glia-derived cells were induced to express rhodopsin exclusively. These rhodopsin-positive cells exhibited synaptophysin around them, suggesting possible formation of synapses. After transplanted in to damaged retina, Müller glia migrated, grafted in host retina and produced rhodopsin. These results suggest that degeneration may promote preferential differentiation of Müller glia to photoreceptors and provide a potential therapeutic strategy for retinal degenerative diseases.
authors.affiliation: Department of Anatomy, Histology and Embryology, Shanghai Medical School, Fudan University, 200032 Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wan
authors.forename: Hua
authors.initials: H
authors.lastname: Zheng
authors.forename: Zu-Lin
authors.initials: ZL
authors.lastname: Chen
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Xiao
authors.forename: Zhen-Jue
authors.initials: ZJ
authors.lastname: Shen
authors.forename: Guo-Min
authors.initials: GM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D056741:Cyclin D; D056743:Cyclin D3; D016213:Cyclins / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000503:physiopathology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008770:Methylnitrosourea; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology* / Q000637:transplantation; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D012243:Rhodopsin / Q000378:metabolism
chemical_list: C534697:Ccnd3 protein, mouse; C534698:Ccnd3 protein, rat; D056741:Cyclin D; D056743:Cyclin D3; D016213:Cyclins; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D008770:Methylnitrosourea; D012243:Rhodopsin