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David Culp, Grazia Spiga, Justin Prater, Brian C Gilger; Characterization of a quantitative model of corneal transplantation in the rabbit. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4370. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To develop and characterize a sensitive and translatable model of corneal transplantation in the New Zealand White Rabbit (NZW).
A 7-mm diameter vacuum trephine was used on the central cornea of NZW recipient eyes, and a 7.5-mm trephine was used to create donor corneas from NZW and Dutch Belted (DB) rabbits. Dexamethasone (DEX) or control were administered topically 3 times a day for 28 days after grafting. Hackett-McDonald (HM) ocular inflammatory scores, rejection index scores, and corneal thickness measurements using spectral domain-optical coherence tomography (SD-OCT, Envisu, Leica) were evaluated on days 1, 3, 5, 7, then weekly through day 28. Corneal endothelial cell (CEC) counts were measured by confocal microscopy (HRT-3, Heidelberg) weekly, and histopathology was done on all grafted eyes at the conclusion of the study.
Cumulative HM scores and rejection index scores were significantly lower (P<0.05) in eyes treated with DEX compared to control on day 3, and remained lower throughout the course of the study. By day 21 more than 50% of control treated eyes had rejected their grafts (rejection index >6), while none of the dex treated eyes rejected by day 28. Corneal thickness measurements, both central and peripheral, were significantly lower (P<0.05) on day 1 in Dex treated eyes, and remained lower than control treated eyes throughout the course of the study. Endothelial cell integrity was significantly better in DEX treated eyes throughout the study, and histologic scores were consistently lower in DEX treated eyes compared to control on day 28.
Using this corneal transplantation model, we demonstrated that topical DEX inhibited ocular inflammation and prolonged rejection compared to control treated eyes. This corneal transplantation model allows quantitative assessment of specific anti-inflammatory and rejection prevention therapies, and can be used in pre-clinical development to provide effective proof of concept of novel compounds or delivery methods.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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