Utilizing Conjoined Mice Models to Explore the Aging Lacrimal Gland



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Aging is a risk factor for dry eye disease (DED), an inflammatory abnormality of the ocular surface that results in an uncomfortable gritty feeling in the eye. It occurs due to significantly reduced tear volume or alteration of tear osmolarity. With a rapidly increasing aging population in the U.S., there is a pressing need to explore DED across age. The lacrimal gland (LG) is responsible for tear production and is affected in DED. This study aimed to explore whether there was a relationship between aged circulating, systemic factors and the LG. Male and female PepBoy mice that were 4 months of age were surgically joined to another same-sex PepBoy or C57BL/6J (B6) mouse, which was aged 18 months. Pairings were either isochronic (young with young or aged with aged) or heterochronic (young with aged). LGs were evaluated 2 months post-surgery. Measurements of T cell and B cell inflammatory marker levels showed a significant upregulation in fold expression of Cd19, Cxc19, Cxcl13, Ifng, Ctss, and Il-1b between both isochronic pairings. Among males, results showed that young, heterochronic mice had significantly greater LG lymphocyte infiltration compared to young, isochronic mice. Intriguingly, we observed significant fibrosis in 36% of the aged parabiotic male LGs, regardless of pairing. In essence, young circulating factors were insufficient in rejuvenating aged mice LGs in the heterochronic pairings. However, aged circulating factors accelerated aging in young mice LGs, thus underscoring the role of systemic, circulating factors in LG insult and DED incidence.