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Published on: May 11, 2015
Microglia-mediated IGF-I neuroprotection in the rd10 mouse model of retinitis pigmentosa
Ana I Arroba1, Noemí Alvarez-Lindo, Nico van Rooijen
13D Lab (Development, Differentiation and Degeneration), Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Purpose:
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.
Insights
Insulin-like growth factor-I (IGF-I) reduces photoreceptor cell death in the rd10 mouse model of retinitis pigmentosa. Microglia are essential for IGF-I's neuroprotective effects, though they also play a detrimental role.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Retinitis pigmentosa (RP) is a group of inherited retinal diseases.
- The rd10 mouse is a common model for studying RP, exhibiting photoreceptor degeneration.
- Microglia play complex roles in retinal inflammation and neurodegeneration.
Purpose of the Study:
- To investigate the neuroprotective effects of Insulin-like Growth Factor-I (IGF-I) in the rd10 mouse model of retinitis pigmentosa.
- To elucidate the role of microglia in the context of IGF-I treatment and photoreceptor cell death.
Main Methods:
- Organotypic retinal explants and intravitreal injections were used to administer IGF-I.
- Photoreceptor cell death was quantified using TUNEL staining and ELISA for free nucleosomes.
- Microglial cells were identified and quantified using Cd11b and Iba1 immunolabeling.
- Microglia depletion was achieved using clodronate-loaded liposomes in cultured retinal explants.
Main Results:
- IGF-I treatment significantly reduced photoreceptor cell death in both ex vivo and in vivo rd10 mouse models.
- IGF-I administration increased microglial cell numbers in the outer nuclear layer (ONL) of explants.
- Depletion of microglia attenuated the neuroprotective effects of IGF-I, indicating their necessity for this benefit.
- Microglia depletion alone also moderately reduced photoreceptor cell death in untreated rd10 retinas.
Conclusions:
- IGF-I demonstrates significant neuroprotective potential against photoreceptor degeneration in the rd10 mouse model of retinitis pigmentosa.
- Microglia are crucial mediators of IGF-I's neuroprotective actions in the dystrophic retina.
- While essential for IGF-I's benefits, microglia also appear to exert a detrimental influence on photoreceptor survival in this model.