Exploring the Transformative Effects of Calorie Restriction on the Lacrimal Gland in Adult Mice

Dry eye disease affects millions worldwide and can result from age-related lacrimal gland (LG) dysfunction, which correlates with a decline in LG secretory cell function and chronic inflammation. This study investigates the potential of calorie restriction (CR) to maintain LG and ocular surface health. Female C57BL/6J mice were subjected to 40% CR for 4 months (start age 6/7 until 10/11M) and compared to mice receiving food ad libitum (AL). LGs bulk RNA sequencing was performed, and fastq files were uploaded on ROSALIND® for processing. Differentially Expressed Genes (DEGs) were analyzed in Metascape to identify the biological pathways significantly modified by CR, and findings were validated. RNA sequencing of LGs subjected to CR compared to ad libitum revealed 589 significant DEGs, with 259 downregulated and 330 upregulatedPathways enriched in upregulated DEGs suggested increase in secretory functions and lipid metabolism, while pathways enriched in downregulated DEGs are related to immune cell activation, the adaptive immune system, extracellular matrix remodeling, and metalloproteinases. These changes were validated by individual qPCR. CR also decreased the age-related dry eye phenotype compared to the ad libitum group. Our results suggest that CR can maintain the health of the LG and ocular surface by reducing inflammation and supporting the LG's secretory function. Overall design: To assess whether CR can slow down inflammation in the LG of adult mice, 6/7M mice were assigned to either an AL or a 40% CR for four months. At 10/11M of age, the mice were euthanized. To determine the genes affected by CR in the LG, we compared the transcriptomes of mice subjected to CR (n = 4) with those fed an AL diet (n = 4) using bulk RNA sequencing of LGs.