• Ivan Mirković, Tamara Kralj, Marin Lozić, Vasilije Stambolija, Josip Kovačević, Luka Vrdoljak, Mirna Zlatar, Kristina Milanović, Domagoj Drmić, Jurica Predović, Sanja Masnec, Matija Jurjević, Mladen Bušić, Sven Seiwerth, Antonio Kokot, and Predrag Sikirić.
• 1Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia; 2Department of Anatomy and Neuroscience, Osijek Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 3Department of Ophthalmology, Sveti Duh University Hospital, Zagreb, Croatia; 4Department of Ophthalmology, Zagreb University Hospital Centre, Zagreb, Croatia.
• Acta Clin Croat. 2020 Sep 1; 59 (3): 394-406.

AbstractWe focused on the relationship of 0.5% tetracaine- and 0.4% oxybuprocaine-induced corneal anesthesia in rats, and pentadecapeptide BPC 157 (0.4 µg/eye), along with nitric oxide synthase (NOS) inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME) (0.1 mg/eye) and/or NOS substrate L-arginine (2 mg/eye), applied in the form of eye drops. We assessed corneal sensitivity recovery (Cochet-Bonnet esthesiometer), corneal lesion elimination (staining with 10% fluorescein) and decrease in tear volume (Schirmer test). BPC 157 administration had a full counteracting effect. Recovery also occurred in the presence of NOS blockade and NOS substrate application. L-arginine eventually shortened duration of corneal insensitivity and exerted corneal lesion counteraction (and counteraction of tetracaine-induced decrease of tear volume) only in earlier but not in later period. L-NAME application led to longer duration of corneal insensitivity, increase in corneal lesions and decrease in tear volume. When L-NAME and L-arginine were applied together, they antagonized each other's effect. These distinctions may indicate particular NOS involvement (corneal insensitivity vs. corneal lesion along with tear production), distinctively affected by the administration of NO agents. However, additional BPC 157 co-administration would re-establish counteraction over topical ophthalmic anesthetic-induced effect, be it in its early or late course. We suggest BPC 157 as an antidote to topical ophthalmic anesthetics.

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