Presence of Histatin-1 in Human Tears and Association with Aqueous Deficient Dry Eye Diagnosis: A Preliminary Study

Sushma Kalmodia,Vinay Kumar Aakalu,Sandeep Jain,Marwan Ali,Bao-Shiang Lee,Bayasgalan Surenkhuu,Dingcai Cao,Arun Balasubramaniam,Kyung-No Son,Dhara Shah

doi:10.1038/s41598-019-46623-9

Sushma Kalmodia, Vinay Kumar Aakalu + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-46623-9

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Journal: Scientific Reports	Publication Date: Jul 16, 2019
Citations: 20	License type: open-access

Affiliation: University of Illinois at Chicago

Abstract

The aims of this study were to determine if histatin-1 (H1) is present in normal human tears and whether tear levels of H1 varied between normal patients and those with aqueous deficient dry eye disease (ADDE). Patient samples were obtained from 11 normal patients and 11 severe ADDE patients. Relevant patient characteristics, including age, sex, and dry eye disease (DED) diagnostic parameters were collected. Multiple qualitative and quantitative methods were used to compare the concentration of H1 between patient groups. Mixed linear modeling was used to compare H1 levels between groups, and diagnostic performance was assessed using the receiver-operator-characteristic (ROC). ADDE patients had significantly lower H1 concentrations (85.9 ± 63.7 ng/ml) than the normal group (891.6 ± 196.5 ng/ml) (p < 0.001), while controlling for age and sex. ROC analysis indicated that H1 concentration is potentially a biomarker for ADDE (area under curve = 0.96). Reclassification of patients by DED parameters including, Ocular Surface Disease Index (OSDI) (≤13, >13) and Schirmer I (without anesthesia) (<10 mm, ≥10 mm) showed significant differences in H1 level (OSDI, p = 0.004) and Schirmer I ((p = 0.010). In conclusion, this is the first preliminary report of the presence of H1 in human tears. H1 concentrations are lower in ADDE patients and H1 may have diagnostic potential in evaluation ADDE patients.

Highlights

There has been some interest in the potential role of histatin peptides in the ocular surface and the lacrimal functional unit
Consistent with our clinical definition of ADDE, we found that the ADDE group had a significantly lower Schirmer I measurements [1.9 ± 0.8 mm vs. 18.3 ± 2.5 mm, p < 0.001 from t-testing] and higher Ocular Surface Disease Index (OSDI) score (33.8 ± 6.6 vs. 1.9 ± 1.0, p < 0.001 from t-testing) than the normal group (Table 1)
Non-invasive tear breakup time (NITBUT) [(secs), p = 0.392] and National Eye Institute-Corneal Staining Score (NEI-CSS) (0–15), p = 0.3045) were not significantly different between ADDE subgroups (SS and oGVHD) whereas, Meiboscale score (0–4) means were significantly different between SS and ADDE subgroups (SS, 0.4 ± 0.2 and oGVHD 1.1 ± 0.1, p = 0.0202) (Supplementary Table 1)

Summary

Introduction

There has been some interest in the potential role of histatin peptides in the ocular surface and the lacrimal functional unit. H1 is thought to be able to promote epithelial migration, adhesion, barrier integrity and reduces the effects of epithelial-mesenchymal transition promoting agents[19]. Such characteristics, if ascribed to an intrinsic component of the tear film would be important to a healthy ocular surface. Given the increasing evidence that histatin peptides are present in the ocular surface and tear film unit and the evidence that H1 can promote epithelial wound healing[17]. Do the tears of normal patients contain H1? Do the tears of patients with ADDE have diminished levels of histatins?

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Results

Conclusion