Unilateral Acute Anterior Uveitis is Associated with Ipsilateral Changes of the Tear Fluid Proteome Involving the LXR/RXR Pathway

Abstract

Purpose : Uveitis is the fourth most common cause of legal blindness in patients between 20 and 60 years of age. Acute anterior uveitis (AAU) can be misinterpreted as external eye disease by non-ophthalmologist doctors; consequently, referral of patients to ophthalmologists may be delayed. Analysis of tear fluid proteins in AAU patients could represent a novel diagnostic modality to aid in this process. This study aimed at determining if ipsilateral changes in the tear fluid proteome due to AAU can be detected by obtaining tear samples with Schirmer’s strips.

Methods : Five adult patients (three men and two women; age range: 25-77 years) diagnosed with unilateral AAU at the Department of Ophthalmology at Oslo University Hospital were included. Tear fluid samples were obtained by inserting one Schirmer’s strip behind the lower eyelid of each eye for five minutes without anesthesia. To detect changes in the tear fluid proteome of the ipsilateral diseased eye, the healthy contralateral eye served as control. Proteins were identified by liquid chromatography tandem mass spectrometry. Ingenuity Pathway Analysis (IPA) was used to explore biological function. R statistical software was used for statistical analyses.

Results : A total of 222 proteins were identified in the tear fluid samples, of which 75 were present in at least three of the five patients. Of these, nine were at least 1.5-fold increased, and eight were at least 1.5-fold decreased in the diseased eye compared to the healthy eye. APOBEC3A was significantly increased in tear samples from the diseased eye relative to the healthy eye (fold change: 1.43; P=0.04), whereas TGM2 was significantly decreased in the diseased eye (fold change: -1.21; P=0.03). IPA identified the LXR/RXR pathway (P<1.02E^-4) as one of the two ‘Top Canonical Pathways’ and ‘Inflammatory Response’ as one of the top four ‘Diseases and Bio Functions’ affected in all five patients. The top ‘Physiological System Development and Function’ in all patients was ‘Immune Cell Trafficking’.

Conclusions : Schirmer’s strips can be used to detect ipsilateral changes in the tear fluid proteome of patients with unilateral AAU. The inflammation-associated LXR/RXR pathway was among the top canonical pathways involved in all patients. Tear fluid may represent a promising new diagnostic modality for patients with AAU.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.