Preferential regeneration of photoreceptor from Muller glia after retinal degeneration in adult rat

To determine whether photoreceptor degeneration can stimulate Muller 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, Muller 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 Muller glia-derived cells were induced to express rhodopsin exclusively. These rh odopsin-positive cells exhibited synaptophysin around them, suggesting possible formation of synapses. After transplanted in to damaged retina, Muller glia migrated, grafted in host retina and produced rhodopsin. These results suggest that degeneration may promote preferential differentiation of Muller glia to photoreceptors and provide a potential therapeutic strategy for retinal degenerative diseases. (C) 2007 Elsevier Ltd. All rights reserved.