Keratoconjunctivitis Sicca and Conjunctival Antigen-Presenting Cells

• Applicant: Dr. Aytan Musayeva
• Subject Area: Ophthalmology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 432369380

Keratoconjunctivitis sicca (KCS), also known as dry eye syndrome, is a chronic, progressive, inflammatory ocular disease characterized by chronic dryness and inflammation of the corneal and conjunctival surfaces. KCS is one of the most prevalent eye diseases. The pathogenesis includes activation of stress pathways on the ocular surface by desiccation resulting in production of inflammatory cytokines by epithelial cells, intraepithelial lymphocytes and infiltrating CD4+ T cells. It has recently been reported that the number of mature antigen presenting cells (APCs) correlated with disease severity and conjunctival goblet cell loss in patients with KCS related to Sjogren’s syndrome. However, it remains to be established, whether this also applies to more common forms of KCS.The goal of the research project is to test the hypothesis that the number of mature APCs in the conjunctiva correlates with disease severity in patients with KCS. The primary objective is to compare the number of mature APCs in impression cytology samples from patients with KCS and controls and to correlate the findings with markers of clinical severity. Secondary objectives are (1) to compare the numbers of individual subgroups of APCs (dendritic cells, macrophages, monocytes) and correlate these with clinical findings and (2) to compare tear MUC5AC (Mucin 5AC, a major secreted mucin of goblet cells) concentration and the number of goblet cells in impression cytology samples from patients with KCS and controls and to correlate the findings with disease markers.Patients with moderate to severe KCS and healthy control subjects will be examined with regard to symptoms using established questionnaires. Quantity and quality of tear film will be determined by Schirmer’s test, tear meniscus height measurement and fluorescein tear break-up time. MUC5AC concentration in tear protein extracted from Schirmer test strips will be measured by ELISA. Quality of the ocular surface will be assessed by fluorescein and lissamine green staining. Moreover, conjunctival cells will be harvested by impression cytology to measure conjunctival goblet cell density and to evaluate chemokine receptor expression in immune cells with flow cytometry.The findings of the study will enhance our understanding of the pathophysiology of KCS by determining if maturation of certain APC populations is associated with goblet cell loss and clinical severity. Discovering biomarkers with greater disease specificity will represent a major advance in diagnostic classification. Moreover, the findings of the study may become helpful to monitor disease progression and to verify the efficacy or the possible toxicity of the therapeutic regimen.

• DFG Programme: Research Fellowships
• International Connection: USA
• Hosts: Professor Dr. Reza Dana; Professor Dr. Stephen Pflugfelder