Microglia-mediated IGF-I neuroprotection in the rd10 mouse model of retinitis pigmentosa.
OBJECTIVE
To characterize the effect of IGF-I in the rd10 mouse model of retinitis pigmentosa at the cellular level, focusing on the role of microglia in the neurodegenerative process.


METHODS
Both organotypic retinal explants and intravitreal injections were used to assess the effect of IGF-I on photoreceptor cell death in the Pde6b(rd10) mice. Cell death was determined by TUNEL in retinal sections and by ELISA of free nucleosomes in retinal extracts. The number and distribution of microglial cells was visualized by immunolabeling with Cd11b and Iba1 antibodies. Depletion of microglia in culture was achieved by treatment with liposomes containing clodronate.


RESULTS
Both ex vivo and in vivo IGF-I treatment reduced the number of TUNEL-positive nuclei in rd10 mouse retinas. In addition, IGF-I treatment in explants increased the number of microglial cells in the ONL. Depletion of microglia in explants with liposomes containing clodronate diminished the neuroprotective effect of IGF-I but also moderately reduced photoreceptor cell death in rd10 retinas cultured in the absence of IGF-I.


CONCLUSIONS
IGF-I is able to attenuate photoreceptor cell death both ex vivo and in vivo in the rd10 mouse retina. Microglia is required for the neuroprotective effect of IGF-I in the dystrophic retina. In addition, microglial cells play a detrimental role, seemingly led to neuroprotection by IGF-I.
3D Lab (Development, Differentiation and Degeneration), Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Ana I
AI
Arroba
Noemí
N
Alvarez-Lindo
Nico
N
van Rooijen
Enrique J
EJ
de la Rosa
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D058449:Intravitreal Injections; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000502:physiology*; D018613:Microscopy, Confocal; D020125:Mutation, Missense; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
C491049:Aif1 protein, mouse; D039481:CD11b Antigen; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D004002:Clodronic Acid; D007334:Insulin-Like Growth Factor I; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse