{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:23:56Z","timestamp":1790796236895,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pandorum Technologies Pvt. Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Purpose: Chemical eye injury is an acute emergency that can result in vision loss. Neurotrophic keratitis (NK) is the most common long-term manifestation of chemical injury. NK due to alkali burn affects ocular surface health and is one of its most common causes. Here, we established a rabbit model of corneal alkali burns to evaluate the severity of NK-associated changes. Material methods: Alkali burns were induced in NZ rabbits by treating the cornea with (i) a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (Mild NK) and (ii) trephination using a guarded trephine (5 mm diameter and 150-micron depth), followed by alkali burn, with a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (a severe form of NK). Immediately after, the cornea was rinsed with 10 mL of normal saline to remove traces of NaOH. Clinical features were evaluated on Day 0, Day 1, Day 7, Day 15, and Day 21 post-alkali burn using a slit lamp, Pentacam, and anterior segment optical coherence tomography (AS-OCT). NK-like changes in epithelium, sub-basal nerve plexus, and stroma were observed using in vivo confocal microscopy (IVCM), and corneal sensation were measured using an aesthesiometer post alkali injury. After 21 days, pro-inflammatory cytokines were evaluated for inflammation through ELISA. Results: Trephination followed by alkali burn resulted in the loss of epithelial layers (manifested using fluorescein stain), extensive edema, and increased corneal thickness (550 \u00b5m compared to 380 \u00b5m thickness of control) evaluated through AS-OCT and increased opacity score in alkali-treated rabbit (80 compared to 16 controls). IVCM images showed complete loss of nerve fibers, which failed to regenerate over 30 days, and loss of corneal sensation\u2014conditions associated with NK. Cytokines evaluation of IL6, VEGF, and MMP9 indicated an increased angiogenic and pro-inflammatory milieu compared to the milder form of NK and the control. Discussion: Using clinical parameters, we demonstrated that the alkali-treated rabbit model depicts features of NK. Using IVCM in the NaOH burn animal model, we demonstrated a complete loss of nerve fibers with poor self-healing capability associated with sub-basal nerve degeneration and compromised corneal sensation. This pre-clinical rabbit model has implications for future pre-clinical research in neurotrophic keratitis.<\/jats:p>","DOI":"10.3390\/cells13050379","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T11:28:47Z","timestamp":1708601327000},"page":"379","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Chemical (Alkali) Burn-Induced Neurotrophic Keratitis Model in New Zealand Rabbit Investigated Using Medical Clinical Readouts and In Vivo Confocal Microscopy (IVCM)"],"prefix":"10.3390","volume":"13","author":[{"given":"Mehak","family":"Vohra","sequence":"first","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"},{"name":"Pandorum Technologies Pvt. Ltd., Bangalore 560100, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abha","family":"Gour","sequence":"additional","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Rajput","sequence":"additional","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"},{"name":"Pandorum Technologies Pvt. Ltd., Bangalore 560100, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharti","family":"Sangwan","sequence":"additional","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"},{"name":"Pandorum Technologies Pvt. Ltd., Bangalore 560100, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Chauhan","sequence":"additional","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"},{"name":"Pandorum Technologies Pvt. Ltd., Bangalore 560100, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartik","family":"Goel","sequence":"additional","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"},{"name":"Pandorum Technologies Pvt. Ltd., Bangalore 560100, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajith","family":"Kamath","sequence":"additional","affiliation":[{"name":"Pandorum Technologies Pvt. Ltd., Bangalore 560100, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umang","family":"Mathur","sequence":"additional","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Chandru","sequence":"additional","affiliation":[{"name":"Pandorum Technologies Pvt. Ltd., Bangalore 560100, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virender Singh","family":"Sangwan","sequence":"additional","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuhin","family":"Bhowmick","sequence":"additional","affiliation":[{"name":"Pandorum Technologies Pvt. Ltd., Bangalore 560100, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Shroff-Pandorum Center for Ocular Regeneration, Dr. Shroff\u2019s Charity Eye Hospital, New Delhi 110002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2147\/EB.S117261","article-title":"Neurotrophic keratitis: Current challenges and future prospects","volume":"10","author":"Versura","year":"2018","journal-title":"Eye Brain"},{"key":"ref_2","unstructured":"(2023, October 04). Neurotrophic Keratitis|Eye. 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