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Published on: November 11, 2017
Autophagy resolves early retinal inflammation in Igf1-deficient mice
Ana I Arroba1, Lourdes Rodríguez-de la Rosa2, Silvia Murillo-Cuesta2
1Alberto Sols Biomedical Research Institute (IIBm) (CSIC/UAM), 28029, Madrid, Spain Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERdem), ISCIII, 28029, Madrid, Spain aarroba@iib.uam.es avalverde@iib.uam.es.
Insulin-like growth factor-1 (IGF-1) deficiency in mice leads to age-related vision loss and retinal inflammation. Autophagy initially protects the retina, but later declines, allowing inflammasome activation and microglial changes.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Insulin-like growth factor-1 (IGF-1) has critical roles in cellular functions and possesses anti-inflammatory properties in the nervous system.
- IGF-1 deficiency in mice (Igf1(-/-)) results in age-related visual impairment and retinal structural changes.
- Autophagy is increasingly recognized for its involvement in immune responses and inflammation.
Purpose of the Study:
- To investigate the interplay between IGF-1 deficiency, retinal aging, inflammation, and autophagy.
- To elucidate the mechanisms underlying age-related visual loss in Igf1(-/-) mice.
Main Methods:
- Analysis of inflammatory markers (Tnfa, Il1b), MAPK phosphorylation (JNK, p38), and autophagy mediators (Becn1, Atg9, Atg5, Atg4, p62, LC3) in Igf1(-/-) mouse retinas.
- Assessment of inflammasome activation (Nlrp3, caspase-1) and microglial activation (Cd11b, Iba-1) in aged Igf1(-/-) retinas.
- Evaluation of reactive gliosis in the retinas of Igf1(-/-) mice.
Main Results:
- Elevated inflammatory markers and MAPK phosphorylation in young and aged Igf1(-/-) retinas.
- Initially active autophagic flux in 6-month-old Igf1(-/-) retinas, followed by decreased flux and inflammasome activation in 12-month-old mice.
- Increased activated microglia and reactive gliosis in the retinas of aged, blind Igf1(-/-) mice.
Conclusions:
- Autophagy acts as an adaptive response to mitigate retinal inflammation in early stages of IGF-1 deficiency.
- Dysregulation of autophagy and subsequent inflammasome activation contribute to age-related retinal degeneration in the absence of IGF-1.
- IGF-1 deficiency exacerbates age-related retinal inflammation and visual loss through impaired autophagy and activated microglia.
