Identification of a Translatable Animal Model for Dry Eye Disease Using Comparative Analysis of Tear Proteins Across Species.

Objective: This study aimed to assess the similarity of tear proteins between experimental animals and humans to identify the most translational animal model for dry eye disease (DED).

Methods: Eleven species were selected for a structural and physicochemical comparison of healthy human tear fluid proteins involved in DED. Amino acid sequences were compared using BLAST. Protein primary structure, isoelectric point (pI) and grand average of hydropathicity (GRAVY) were determined using ExPASy and compared with humans.

Results: Among non-primate mammals, the cat (69.7%) and pig (68.7%) showed the highest protein sequence similarity to humans. The ruminants and cat showed amino acid content changes for the highest number of proteins (≥3/15). The pig, rabbit, dog and rodents had the closest global pI values to humans, while the cat showed the highest protein number (9/15) with pI values far from humans. GRAVY values for the pig and dog were the closest to humans. Tear-soluble factor study revealed that the pig was the only species with high similarity for all proteins (>60%). Amino acid content was similar for most species compared to humans, except mouse for IL-6 and rodents and pig for IL-8. The pI and GRAVY values varied across species, though the pig and sheep were the only ones with similar pI to humans for four out of five factors.

Conclusions: The pig exhibited the highest similarity to humans in tear protein analysis among non-primate mammals, suggesting that the porcine model may be the most translational for DED research.