Age-Related Upregulation and Strong Expression Correlation of the Proinflammatory Cytokines IL-1β and IL-6 Across Multiple Segments of the Mouse Eye

Abstract

Emerging evidence suggests that ocular inflammation increases with age and is associated with various disease states. That said, the majority of studies suffer from a significant limitation--they only focus on a single segment of the eye. This represents a limitation because age-related increases in neuroinflammatory markers are not necessarily uniform within an organ, and other age-related changes in the eye are known to occur in a segment-specific manner. The present study aims to address this gap by comparting/contrasting age-related changes in the proinflammatory cytokines IL-6 and IL-1{beta} across multiple mouse ocular segments: the (i) anterior segment (i.e., cornea, ciliary body and muscle, and zonules), (ii) retina, and (iii) posterior segment (i.e., sclera, choroid, Bruchs membrane, retinal pigmented epithelium, and parts of the optic nerve). IL-6 and IL-1{beta} were selected as targets since they exhibit differential regional patterns of age-related increases within the brain. Eyes were collected on postnatal days (P) P28, P56, P98, P200 and P500 and processed by Western blot. Both IL-6 and IL-1{beta} protein levels increased across the lifespan in all three eye segments. Interestingly, correlational analyses revealed that IL-1{beta} and IL-6 expression correlated with each other not only within individual eye segments, but also across segments. In old mice, IL-1{beta} and IL-6 levels also correlated with expression of phosphodiesterase 11A (PDE11A), an enzyme known to regulate neuroinflammation. Together, these findings suggest that inflammaging in the eye is broadly controlled by a systemic governor, unlike the brain that shows region-specific changes in cytokines with age.