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J.L. Vittitow, W.A. Eckert, III, J.A. Ezzell, R.S. Verhoeven, W.M. Peterson, S.A. Anderson; An Experimental Model of Chronic Dry Eye Combining Extraorbital Lacrimal Gland Excision and Subcutaneous Scopolamine in the Rat . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5598.
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Previous work in rats has demonstrated that removal of the extraorbital lacrimal gland results in decreased tear volume. However, significant ocular surface damage is minimal. The objective of this study was to development a clinically relevant rapid onset rat model of dry eye by combining lacrimal gland excision and scopolamine to promote ocular surface damage.
Sixty 6–week old male Sprague Dawley rats were housed for 8 weeks in a controlled–environment room, with 30–35% relative humidity and 20–24 oC temperature. Following randomization (based on tear volume), 40 rats (4 groups; n=10/group) underwent bilateral lacrimal gland excision (ExLac). Three of the ExLac groups received subcutaneous scopolamine (scop) injections (15 mg/kg) 1x/day (ExLacQD), 2x/day (ExLacBID) or 3x/day (ExLacTID). One group did not receive scop (ExLac0). The remaining 20 animals served as non–surgical controls and did not receive scop. Aqueous tear volume (TV) was measured twice per week using phenol cotton threads while corneal fluorescein (F) staining was measured once per week (scale 0–6). Tear clearance measurements were taken at weeks 2, 4, 6 and 8.
A significant decrease in TV was seen by study day 6 in all ExLac groups compared to control. Additionally, rats receiving subcutaneous scop injections (ExLacS) had significantly decreased TV as compared to ExLac0 (ExLacTID 2.9±0.4mm, ExLacBID 3.75±0.21mm, ExLacQD 3.97±0.4mm vs ExLac0 4.8±0.18mm; p<0.05). These decreased TV levels remained relatively constant through study day 57. Corneal F staining was significantly increased for the ExLac0 group vs. control at day 9 (1.0±0.01 vs 0.27±0.05; p<0.05) and remained constant throughout the study. ExLacS groups had significantly increased corneal F staining vs both control and ExLac0 throughout the study. The average F staining score in the ExLacS animals at day 9 was 2.46±0.26 and staining steadily increased to 4.8±0.36 by day 57. No significant differences were observed in TV or corneal F staining between ExLacQD, ExLacBID, and ExLacTID. Tear clearance was significantly decreased in all ExLacS groups compared to control and ExLac0 at all time points measured.
Lacrimal gland removal alone results in moderate tear volume reductions and mild ocular surface damage. Subcutaneous scop in addition to lacrimal excision produces a model with significant ocular surface drying and robust corneal staining within a week. The phenotype continues to develop over time suggesting a clinically relevant dry eye model for pathophysiologic and pharmacologic studies.
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