Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjögren syndrome

PURPOSE. To determine whether the relative amounts of mucin mRNA in the conjunctival epithelium and mucin protein in the tears are altered in patients with Sjogren syndrome compared with healthy individuals. METHODS. Tear fluid was collected from the inferior fornix of normal subjects (n 17) and patients with Sjogren syndrome (n 11) after instillation of 60 L sterile water onto the ocular surface. Immediately after tear fluid collection, conjunctival epithelium was obtained by filter paper-stripping from the bulbar temporal region for mRNA isolation. Primers to nontan- dem repeat sequences of the gel-forming mucin MUC5AC and the membrane-spanning mucins MUC1 and MUC4 were used in real-time RT-PCR to determine relative abundance of MUC mRNA in patients with Sjogren syndrome in relation to that of normal subjects. Enzyme-linked immunosorbent assay was per- formed on neuraminidase-treated tears, using a polyclonal an- tibody against a synthetic peptide mimicking the deduced amino acid sequence from the D3 region of MUC5AC. RESULTS. The number of RNA transcripts for the goblet cell- specific mucin MUC5AC in the conjunctival epithelium of patients with Sjogren syndrome was significantly lower than in normal individuals. No significant changes were detected when analyzing the mRNA levels of the mucins expressed by the stratified epithelium of the conjunctiva, MUC1 and MUC4. Protein levels of the goblet cell mucin MUC5AC were signifi- cantly reduced in the tear fluid of patients with Sjogren syn- drome, corroborating mRNA data obtained using real-time RT- PCR. CONCLUSIONS. The tear fluid of patients with Sjogren syndrome has reduced levels of the goblet cell-specific mucin MUC5AC, which correlates to decreased levels of conjunctival MUC5AC mRNA. The authors propose that deficiency of MUC5AC mucin in tears constitutes one of the mechanisms responsible for tear film instability in Sjogren syndrome. (Invest Ophthalmol Vis Sci. 2002;43:1004 -1011)