Sanjay Marasini1, Odunayo O Mugisho2, Simon Swift3, Hannah Read3, Ilva D Rupenthal2, Simon J Dean1, Jennifer P Craig4. 1. Ocular Surface Laboratory, Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, New Zealand. 2. Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, New Zealand. 3. Department of Molecular Medicine and Pathology, The University of Auckland, New Zealand. 4. Ocular Surface Laboratory, Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, New Zealand. Electronic address: jp.craig@auckland.ac.nz.
Abstract
PURPOSE: Antimicrobial ultraviolet C (UVC) has proven efficacy in vitro against keratitis isolates and has potential to treat corneal infection if safety can be confirmed. METHOD: Safety of 265 nm, 1.93 mW/cm2 intensity UVC (15-300 s exposures) was investigated in vitro via cyclobutane pyrimidine dimer (CPD) formation in DNA of human cultured corneal epithelial cells; ex vivo, by evaluating UVC transmissibility as a function of porcine corneal thickness; and in vivo, by evaluating CPD induction in the mouse cornea following UVC exposure. RESULTS: A single exposure of 15 s UVC did not induce significant CPD formation (0.92 ± 1.45%) in vitro relative to untreated control (p = 0.93) whereas 300 s exposure caused extensive CPD formation (86.8 ± 13.73%; p < 0.0001). Cumulative exposure to 15 s UVC daily for 3 days induced more CPD (14.6 ± 8.2%) than a single equivalent 45 s exposure (8.3 ± 4.0%) (p < 0.001) but levels returned to baseline within 72 h (p = 0.29), indicating highly efficient DNA repair. Ex vivo, UVC transmission decreased sharply with increasing corneal thickness, confirming UVC effects are limited to the superficial corneal layers. In vivo evaluations demonstrated no detectable CPD after three consecutive daily 15 s UVC exposures, whereas a single 300 s exposure induced extensive CPD formation in superficial corneal epithelium. CONCLUSION: Up to three daily doses of 15 s UVC, in vivo, appear safe with respect to CPD formation. Ongoing research exploring UVC as a possible treatment for microbial keratitis is warranted.
PURPOSE: Antimicrobial ultraviolet C (UVC) has proven efficacy in vitro against keratitis isolates and has potential to treat corneal infection if safety can be confirmed. METHOD: Safety of 265 nm, 1.93 mW/cm2 intensity UVC (15-300 s exposures) was investigated in vitro via cyclobutane pyrimidine dimer (CPD) formation in DNA of human cultured corneal epithelial cells; ex vivo, by evaluating UVC transmissibility as a function of porcine corneal thickness; and in vivo, by evaluating CPD induction in the mouse cornea following UVC exposure. RESULTS: A single exposure of 15 s UVC did not induce significant CPD formation (0.92 ± 1.45%) in vitro relative to untreated control (p = 0.93) whereas 300 s exposure caused extensive CPD formation (86.8 ± 13.73%; p < 0.0001). Cumulative exposure to 15 s UVC daily for 3 days induced more CPD (14.6 ± 8.2%) than a single equivalent 45 s exposure (8.3 ± 4.0%) (p < 0.001) but levels returned to baseline within 72 h (p = 0.29), indicating highly efficient DNA repair. Ex vivo, UVC transmission decreased sharply with increasing corneal thickness, confirming UVC effects are limited to the superficial corneal layers. In vivo evaluations demonstrated no detectable CPD after three consecutive daily 15 s UVC exposures, whereas a single 300 s exposure induced extensive CPD formation in superficial corneal epithelium. CONCLUSION: Up to three daily doses of 15 s UVC, in vivo, appear safe with respect to CPD formation. Ongoing research exploring UVC as a possible treatment for microbial keratitis is warranted.
Authors: Darren Shu Jeng Ting; Jessica Cairns; Bhavesh P Gopal; Charlotte Shan Ho; Lazar Krstic; Ahmad Elsahn; Michelle Lister; Dalia G Said; Harminder S Dua Journal: Front Med (Lausanne) Date: 2021-08-11