Development and validation of a reliable rabbit model of limbal stem cell deficiency by mechanical debridement using an ophthalmic burr

Vijay Kumar Singh, Abhinav Reddy Kethiri, Tejaswini Pingali, Abhishek Sahoo, Mohd Salman, Madhuri Amulya Koduri, Deeksha Prasad, Kiran Kumar Bokara, Sayan Basu, Vivek Singh

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    A simple and reproducible method is necessary to generate reliable animal models of limbal stem cell deficiency (LSCD) for assessing the safety and efficacy of new therapeutic modalities. This study aimed to develop and validate a rabbit model of LSCD through mechanical injury. The corneal and limbal epithelium of New Zealand White rabbits (n = 18) were mechanically debrided using an ophthalmic burr (Algerbrush II) with a 1.0-mm rotating head after 360° conjunctival peritomy. The debrided eyes were serially evaluated for changes in corneal opacity, neo-vascularization, epithelial defect and corneal thickness using clinical photography, slit lamp imaging, fluorescein staining, and anterior segment optical coherence tomography scanning (AS-OCT). Following this, an assessment of histopathology and phenotypic marker expression of the excised corneas was conducted. The experimental eyes were grouped as mild (n = 4), moderate (n = 10), and severe (n = 4) based on the grade of LSCD. The moderate group exhibited abnormal epithelium, cellular infiltration in the stroma, and vascularization in the central, peripheral, and limbal regions of the cornea. The severe group demonstrated central epithelial edema, peripheral epithelial thinning with sparse goblet cell population, extensive cellular infiltration in the stroma, and dense vascularization in the limbal region of the cornea. A significant decrease in the expression of K12 and p63 (p < 0.0001) was observed, indicating the loss of corneal epithelium and limbal epithelial stem cells in the LSCD cornea. This study demonstrates that the Alger brush-induced mechanical debridement model provides a reliable model of LSCD with comprehensive clinic-pathological features and that is well suited for evaluating novel therapeutic and regenerative approaches.

    Original languageEnglish
    Article number109667
    Number of pages8
    JournalExperimental Eye Research
    Volume236
    DOIs
    Publication statusPublished - Nov 2023
    Publication typeA1 Journal article-refereed

    Keywords

    • Algerbrush
    • Animal Model
    • Limbal Stem Cell Deficiency
    • LSCD
    • Mechanical Debridement

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Ophthalmology
    • Sensory Systems
    • Cellular and Molecular Neuroscience

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