Innate immunity in age-related retinal degeneration
Summary
Purpose
Ageing is a major risk factor for the development of multifactorial ocular conditions like glaucoma, diabetic retinopathy and age-related macular degeneration. We aim to understand how its influence on the innate immune system may contribute to increased morbidity of retinal degenerations with age.
Methods
Changes in expression of cytokines, chemokines and complement genes in response to ageing, laser-injury or light were determined in young (2–4 months) and aged (18–24 months) wildtype, chemokine (Ccl2−/−) and complement regulator (CD59a−/−) deficient mice and correlated with myeloid cell populations and histology of the retina and the RPE-choroid.
Results
Ageing promotes pro-inflammatory Ccl2-Ccr2 signalling and up-regulation of complement genes in particular in the choroid. Genetic ablation of Ccl2 attenuates these age-related inflammatory changes and is associated with reduced recruitment of pro-inflammatory myeloid cells and a reduced CNV response. Deficiency of CD59a enhances complement activation but not pathology.
Conclusion
Age-related innate immune activation by Ccl2 or by complement can promote ocular pathology, and may represent common mechanisms for enhanced pathology in age-related inflammatory diseases.
