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Margarita Calonge, Sara Galindo, Teresa Nieto-Miguel, Marina Lopez- Paniagua, Ana de la Mata, María Plata-Cordero, Esther Rey, Jose Maria Herreras; Ocular Surface Inflammation in an Experimental Model of Partial and Total Limbal Stem Cell Deficiency. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5638.
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© ARVO (1962-2015); The Authors (2016-present)
Management of ocular surface inflammation and epithelial restoration after ocular surface failure due to partial or total limbal stem cell deficiency (LSCD) is a great challenge. It is then essential to develop animal models that resemble the different grades of LSCD in humans to accurately test the efficacy of new therapies. To this aim, we developed and graded a mild-to-severe model of LSCD-related ocular surface inflammation in rabbits.
After complete corneal epithelial debridement by n-heptanol, a surgical 1800 (partial LSCD) or 3600 (total LSCD) limbal peritomy was performed in one eye of 6 and 10 rabbits, respectively. Corneal neovascularization, opacification, and epithelial defect were clinically scored (0-4 scale) on a weekly basis. Histopathology evaluated the degree of damage, the inflammatory infiltrate, and the number of goblet cells (as a sign of conjunctival in-growth) in the limbus and central cornea, at the end of follow-up (11 weeks).
Rabbit corneas of both partial and total LSCD models developed opacity, epithelial defects and neovascularization during the 3-4 weeks following injury. Corneal opacity and ulceration were significantly higher in the total (2.3 and 2.5, respectively) than in the partial (1.3 and 1.1, respectively) LSCD model and prominent neovessels were only seen in total LSCD; 4 of these 10 rabbits were more severe from the beginning, developing a 3600 thick conjunctivalization, eventually covering the entire cornea. Histology of the corneal and limbal stroma manifested a significantly larger number of infiltrating inflammatory cells and goblet cells and a more disorganized structure in the total LSCD model; the limbal and corneal epithelium was only lost in the total LSCD model. These data demonstrates stratified results: a milder change in the ocular surface was seen in 100% of rabbits undergoing partial LSCD, a moderate ocular surface pathology in 60% of total LSCD rabbits, and a severe outcome in 40% of total LSCD.
An efficient experimental model of inflammation after ocular surface failure due to LSCD was developed. Three progressive grades of severity were observed that closely resemble this human pathology and thus makes this model suitable to test efficacy of novel therapies for the treatment of inflammation due to corneal stem cell pathology before consideration for translation into clinical trials.
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