Gene Expression Changes on the Ocular Surface Cellular Aging

Abstract

Purpose : To examine gene expression changes on the ocular surface associated with aging using middle-aged mice.

Methods : Tear secretion was measured by a phenol red test and corneal fluorescein staining score (CFS) was measured using 0.5% sodium fluorescein and slit-lamp examination respectively, in adult mice (8-12 weeks old, C57BL6, female) and middle-aged mice (48-55 weeks old, C57BL6, female). Samples of corneal, conjunctival, and cervical lymph nodes from each group were collected for the comparative analysis of gene expression in cell markers associated with aging (p16 and p21 variant 2) by real-time PCR, as well as differentially expressed gene (DEG) analysis and Gene Ontology analysis by RNA sequencing.

Results : A significant increase in tear secretion was observed in the middle-aged group compared to the adult group (P=0.023). No significant difference was found in CFS between the two groups. In the middle-aged group, there was an increase in gene expression of p16 in the cornea and cervical lymph nodes (P =0.002 and P =0.039, respectively), and an increase in gene expression of p21 variant 2 in the cervical lymph nodes (P =0.031). DEG analysis by RNA sequencing identified characteristic DEGs of the middle-aged group when compared to control: cornea, 128 genes (up-regulated DEG; 23 genes, down-regulated DEG; 105 genes); conjunctiva, 194 genes (up-regulated DEG; 41 genes, down-regulated DEG; 153 genes); cervical lymph nodes, 678 genes (up-regulated DEG; 385 genes, down-regulated DEG; 293 genes). Gene Ontology analysis identified Go Terms related to extracellular matrix, cell adhesion, angiogenesis regulation, calcification in the cornea; keratinization in the conjunctiva; and extracellular matrix, innate immunity, and mucosal immunity in the cervical lymph nodes in the middle-aged group compared to the adult group.
Conclusion: This study revealed tissue reorganization, cellular interaction, and immune environment changes may be major contributors to cellular aging of the ocular surface.This study revealed tissue reorganization, cellular interaction, and immune environment changes may be major contributors to cellular aging of the ocular surface.

Conclusions : This study revealed tissue reorganization, cellular interaction, and immune environment changes may be major contributors to cellular aging of the ocular surface.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.