Abstract
Purpose :
Aging is associated with inflammation and oxidative stress. In the eye and lacrimal gland (LG), increasing age is associated with chronic inflammation, a greater infiltration of immune cells, and tissue damage. Heterochronic parabiosis is an experimental method used to identify how soluble serum factors impact aging and disease. We investigated if heterochronic pairing of mice (young to aged) could modulate age-related eye and LG alterations.
Methods :
Male and female PepBoy mice 4 months of age were surgically joined to either another PepBoy or a C57BL/6J (B6) mouse aged 18 months. Pairings were either isochronic (young to young or aged to aged) or heterochronic (young to aged), all same-sexed. Mice were evaluated 2 months post-surgery. General appearance and focus score were investigated in H&E-stained LG sections (n=21 male pairs; n=5 female pairs). LGs were analyzed by qPCR for inflammatory and T and B-cell related markers (n=5 male pairs; n= 6 female pairs).
Results :
There were significant increases in focal score in aged-aged pairings compared to young-young pairings (Kruskal-Wallis test; P<0.0001). In male LGs, there was a significant increase in focal score in both mice in the heterochronic young-aged pairing (2±2 vs 3±2 focus score/4mm2) compared to the isochronic young-young and young non-parabiotic (0.8±0.7 and 0±0 focus score/4mm2, respectively, at least P<0.01). There were significant increases in mRNA fold expression of Ctss (3-fold), Ciita (MHC II,3-fold), Cd19 (57-fold), Ccl19 (3.67-fold), and Ifng (IFN-γ,7-fold) by age (young-young vs. aged-aged) in aged female pairs. There were significant sex-related changes in mRNA fold in Cxcl13 (13-fold) and Il1b (2-fold) in isochronic pairs (at least P<0.05 for all). Interestingly, we found significant fibrosis in 36% of the aged parabiotic male LGs, irrespectively of pairing.
Conclusions :
Our results indicate that serum soluble factors from young mice for 8 weeks were not enough to reverse inflammation and infiltrating immune cells in aged tissues. It is possible that a longer duration of parabiosis is needed. This suggests that age-related changes in the LG microenvironmental/architecture participate in perpetuating inflammation. Therapies that aim at improving cellular health may have a stronger impact on improving inflammation and cellular inflammation in LGs than parabiosis.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.