Abstract
Purpose: :
Topical BAK induces ocular surface inflammation and tear film instability. We propose that Corneal Axonopathy is a hitherto unrecognized feature of BAK-induced DED. This study will investigate the role of Corneal Axonopathy in the pathophysiology of DED.
Methods: :
6-8 week old thy1-yellow fluorescent protein (thy1-YFP)-transgenic mice in which corneal nerves express the YFP protein driven by the thy1 promoter were used for this study. Thy1-YFP mice were divided into 2 groups. All mice were administered 0.1% BAK topically in one eye, twice daily for a period of 4 weeks followed by a cessation period of no BAK treatment from week 5-9. The first group (n=10) were anesthetized at day 0 (baseline), day 3 and every week from 1-9 and were evaluated for aqueous tear production measurement (modified Schirmer’s test) and corneal nerves were evaluated by YFP fluorescence imaging. The second group (n=5 mice per time point) were sacrificed at day 0 (baseline) and weeks 2, 4, 7 and 9 and processed for corneal fluorescein labeling, immunofluorescence using axonopathy and inflammation markers, NF-H (SMI-32) and CD11b respectively. Inflammation was also determined by corneal superficial punctate keratopathy (SPK) counts and a Th1/Th2/Th17 cytokine array kit.
Results: :
Two patterns of corneal axonopathy were observed at 1 week of BAK treatment (i) Superficial Axonopathy wherein only the hairpin-like sub-epithelial plexus of nerves were obliterated and (ii) Complete Axonopathy wherein the deeper stromal nerve trunks were also obliterated. Mild inflammation (1-5 YFP positive T-cells per cornea) was associated with superficial axonopathy. Severe inflammation (>10 YFP positive T-cells per cornea) was associated with complete axonopathy. Aqueous tear production was significantly reduced in both patterns of corneal axonopathy. Evidence of nerve remodeling was observed only in superficial axonopathy.
Conclusions: :
Corneal Axonopathy appears to correlate with severity of inflammation and ocular signs of DED (decreased aqueous tear production and surface SPK).
Keywords: cornea: basic science • cornea: stroma and keratocytes • inflammation