Investigating conjunctival immune pathways in Sjögren and non-Sjögren disease associated dry eye.

PURPOSE Dry eye disease (DED) is classified based on its predominant etiology into aqueous tear-deficient (ATD), evaporative, or mixed. Sjӧgren disease keratoconjunctivitis sicca (SjD-KCS) is a very severe autoimmune form of ATD DED. The purpose of this work was to compare transcriptomic changes in the conjunctiva sampled from patients with ATD, SjD-KCS, and healthy controls (HC) to evaluate distinctions in the immune response on the ocular surface based on diagnosis.

METHODS Impression cytology of the temporal bulbar conjunctiva was collected using the EyePrim device. RNA was extracted and submitted with the Nanostring nCounter Human Immunology V2 panel for gene expression analysis. Results were uploaded to ROSALIND and Metascape to identify DEGs by comparison (all DED vs HC; SjD vs HC; ATD vs HC) and associated predicted pathways. A subset of samples (n = 4 per group) were used for immunofluorescent staining of LAMP3 and HLA-DR.

RESULTS 49 patients were enrolled in the study (25 HC; 12 SjD; 12 ATD). 100 DEGs were found in the comparison of all DED vs HC. 69 DEGs were found in the SjD vs HC. 11 DEGs were found in the ATD vs HC. There were no DEGs identified in the SjD vs ATD comparison. DEGs were involved in immune pathways related to viral response, adaptive immunity, and cell to cell communication. DED conjunctiva had increased expression of LAMP3 and HLA-DR compared to HC.

CONCLUSIONS Our findings demonstrate that DED, regardless of the diagnosis, have similar immune-related DEGs and associated pathways on the ocular surface.