Microglia-Müller Glia Crosstalk in the rd10 Mouse Model of Retinitis Pigmentosa
Retinitis pigmentosa refers to a large, genetically heterogeneous group of retinal dystrophies. This condition is characterized by the gradual onset of blindness due to progressive deterioration of the retina, a process that includes photoreceptor and retinal-pigmented-epithelium cell decay and death, microglial recruitment, reactive gliosis, and vascular disorganization and regression. We found that early in the degenerative process, the rd10 mouse retina exhibits high levels of photoreceptor cell death and reactive Müller gliosis. In explant cultures, both degenerative processes were abrogated by IGF-I treatment. Moreover, the beneficial effect of IGF-I was diminished by microglial depletion using clodronate-containing liposomes. Interestingly, in the absence of IGF-I, microglial depletion partially prevented cell death without affecting Müller gliosis. These findings strongly suggest a role for microglia-Müller glia crosstalk in neuroprotection. However, a subpopulation of microglial cells appears to promote neurodegeneration in the dystrophic retina. Our findings indicate that beneficial neuroprotective effects may be achieved through strategies that modulate microglial cell responses.
KeywordsRetinal dystrophy Retinal degeneration Neuroprotection Clodronate IGF-I
EJdelaR was supported by the Spanish Ministerio de Ciencia e Innovación (Grant SAF2010-21879) and the Fundación Médica Mutua Madrileña. AIA was supported by a postdoctoral contract from the Spanish Fondo de Investigaciones Sanitarias. The authors thank Prof. Julio Navascués and Dr. Amanda Sierra for scientific advice, Prof. Flora de Pablo for continuous encouragement and ideas, Dr. Owen Howard for editorial support, and Maite Seisdedos, Ana Robles and the staff of the CIB animal house for technical support.
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