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. 2023 Nov 20;24(22):16510.
doi: 10.3390/ijms242216510.

A Comprehensive Assessment of Tear-Film-Oriented Diagnosis (TFOD) in a Dacryoadenectomy Dry Eye Model

Saki Sakakura  1 , Emi Inagaki  1   2   3 , Yuichiro Ochiai  4 , Masatoshi Yamamoto  4 , Naofumi Takai  4 , Taeko Nagata  1 , Kazunari Higa  5 , Yasunori Sato  6 , Hiroshi Toshida  7 , Dogru Murat  8 , Masatoshi Hirayama  1 , Yoko Ogawa  1 , Kazuno Negishi  1 , Shigeto Shimmura  1   9
Affiliations

A Comprehensive Assessment of Tear-Film-Oriented Diagnosis (TFOD) in a Dacryoadenectomy Dry Eye Model

Saki Sakakura et al. Int J Mol Sci. .

Abstract

Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of tear film instability has made drug development difficult. Although rabbit dry eye models have been reported in the past, there are only a few reports that focus on tear film instability. Herein, we assessed the tear film stability of a rabbit dry eye model induced by dacryoadenectomy. A clinical evaluation of the ocular surface, interferometry, and histological assessments of the cornea and conjunctiva were performed. Following the removal of the lacrimal glands, TBUT was shortened significantly, with dimple and random breakup patterns prominently observed. Furthermore, the blink rate in this model increased after dacryoadenectomy, suggesting that this model partially captured the phenotypes of human short TBUT-type dry eye and may be useful as an animal model for investigating potential drug candidates.

Keywords: animal model; dry eye; dry eye therapy; tear film breakup.

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Conflict of interest statement

Authors E.I. and K.N. have received research grants from Kitayama Labes. Y.O. (Yuichiro Ochiai), M.Y. and N.T. provided the resources, however, the funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results. The remaining authors (S.S. (Saki Sakakura), T.N., K.H., Y.S., H.T., D.M., M.H., Y.O. (Yoko Ogawa), and S.S. (Shigeto Shimmura)) declare no conflict of interest.

Figures

Figure 1
Figure 1
Time course and pattern of tear film breakup time (TBUT). (A) Comparison of TBUT between control and lacrimal gland removal (LGR) eyes at different times (n = 6, *** p < 0.001). (B) The ratio of breakup patterns in LGR eyes. (Six rabbits, a total of 48 eyes in each group, were analyzed from one week after LG removal to the end of the study at eight weeks). (C,D) Breakup pattern of LGR eyes: (C) dimple breakup pattern and (D) random breakup pattern. Arrows indicate breakup. (E) Blink rate (blinks/min) (n = 6, * p = 0.01).
Figure 2
Figure 2
Time course of corneal fluorescein score. There were no significant differences (ns) between control and lacrimal gland removal (LGR) eyes at every experimental period (n = 6).
Figure 3
Figure 3
(A,B) Schirmer’s I test procedure (A) and its time course of control and lacrimal gland removal (LGR) eyes (B) (n = 6). (C–E) Tear meniscus height (TMH) measurement procedure with OSA: (D) high-power field of (C), and (E) time course of control and LGR eyes (n = 6). No significant difference (ns) was detected between control and lacrimal gland removal (LGR) eyes.
Figure 4
Figure 4
(A) Typical images of grading scales using interferometry in rabbits. (B) Results of the ratio of interferometry grading between control and lacrimal gland removal (LGR) eyes. There were no significant differences. (Six rabbits, a total of 54 eyes in each group, were analyzed from pre-treatment to the end of the study at eight weeks).
Figure 5
Figure 5
Histological assessment of cornea and conjunctiva. Scale bars are 100 μm. (A,B) Hematoxylin-eosin (HE) staining of the control (A) and lacrimal gland removal (LGR) cornea (B). (C,D) HE staining of the control (C) and LGR conjunctiva (D). (E,F) PAS staining of the control (E) and LGR conjunctiva (F). (G) The results of PAS-positive cell counts (/mm) in the control and LGR conjunctiva. There was no significant difference (ns) (n = 6).
Figure 6
Figure 6
(A–D) Surgical procedures: removal of the nictitating membrane (A, black arrow), orbital lobe of the superior lacrimal gland (LG) (B, black arrow), palpebral lobe of superior LG (C, black arrow), and inferior LG (D, black arrow). (E) Time course of ocular surface evaluations.
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