International Journal of Molecular Sciences · 14 authors, 9 centres
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This study evaluated a rabbit dry eye model induced by lacrimal gland removal using tear-film-oriented diagnosis (TFOD). The model consistently showed significantly shortened tear film breakup time (TBUT) with dimple and random breakup patterns, mimicking human short TBUT-type dry eye. This model may be useful for developing tear film stabilizing agents and for preclinical drug testing.
**Background:** Dry eye disease is a common ocular condition, and tear film instability is a major cause. Short tear film breakup time (TBUT)-type dry eye is more prevalent than aqueous tear deficiency. However, there is a lack of appropriate animal models focusing on tear film instability, hindering drug development. This study aimed to establish and characterize a rabbit dry eye model induced by dacryoadenectomy using tear-film-oriented diagnosis (TFOD) methods, including non-invasive assessments with the Ocular Surface Analyzer (OSA).
**Methods:** Six female New Zealand white rabbits (12 eyes) were used. The left eye underwent removal of the superior and inferior lacrimal glands and nictitating membrane (LGR group), while the right eye served as the control. Ocular surface evaluations were performed weekly for eight weeks post-surgery. Assessments included: TBUT and breakup patterns (using OSA-Vet), blink rate (from video recordings), corneal fluorescein staining score (0-9 scale), Schirmer's I test (tear volume), tear meniscus height (TMH) by OSA, lipid layer thickness (LLT) grading by interferometry (grades 0-4), and histological examination of cornea and conjunctiva (hematoxylin-eosin and PAS staining). Statistical analysis used generalized linear mixed models and unpaired t-tests.
**Key Results:** One week after lacrimal gland removal, TBUT in LGR eyes (2.9 ± 0.5 s) was significantly shorter than in control eyes (23.5 ± 7.2 s), and this difference persisted for eight weeks (p < 0.001). Breakup patterns in LGR eyes were predominantly random (79%, n=38) and dimple (21%, n=10); area and line breakups were absent. Blink rate increased significantly from 0.2 ± 0.2 blinks/min pre-treatment to 2.3 ± 0.7 blinks/min after dacryoadenectomy (p = 0.01). Corneal fluorescein staining scores were higher in LGR eyes (3.2 ± 0.2 at 8 weeks) compared to controls (1.5 ± 0.5), but the difference was not statistically significant (p = 0.15). Schirmer's I test showed no significant difference between groups (p = 0.78); at 8 weeks, LGR eyes had 12.5 ± 1.0 mm vs. control 17.2 ± 2.5 mm. TMH also did not differ significantly (p = 0.57); at 8 weeks, LGR eyes had 0.16 ± 0.02 mm vs. control 0.23 ± 0.02 mm. LLT grading was similar between groups, with grade 1 being most frequent. Histologically, corneal and conjunctival epithelium appeared normal, and goblet cell density was not significantly different (LGR: 21.4 ± 2.2 cells/mm, control: 22.5 ± 1.2 cells/mm, p = 0.67).
**Clinical Implications:** This rabbit dacryoadenectomy model consistently exhibits short TBUT-type dry eye features, including reduced TBUT, dimple and random breakup patterns, and increased blink rate, without significant aqueous tear deficiency. The model aligns with TFOD principles and TFOS DEWS II recommendations, making it suitable for studying tear film instability and testing potential tear film stabilizing agents. The stable phenotype for up to eight weeks supports its use in preclinical drug development. However, the model does not show all signs of aqueous-tear-deficient dry eye, and further studies are needed to explore mucin expression and tear composition changes.