Keeping an eye on molecular imaging: Assessment of drug toxicity in small ocular structure using Mass Spectrometry Imaging

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Mass spectrometry Imaging (MSI) applications to ophthalmic drug discovery have recently gained growing interest especially for pharmacological or toxicological studies. MSI was applied to assess the distribution of benzalkonium chloride (BAK); a common eye drops preservative, in specific areas of the eye after instillations in animal model tissues. Preservatives have been reported to cause ocular surface disorders with tear film alteration, eye irritation and to promote dry eye. Therefore, BAK distribution was investigated in small specific histological regions of the eyes in New Zealand rabbits in order to estimate the possible localizations of adverse effects of the treatment. Local drug concentration differences were observed according to the histological area and positions on eye cryosections, at anterior, posterior, temporal or nasal sides. MSI and immunohistochemistry results were put side-by-side to correlate inflammatory areas, degradation of corneal epithelium or apoptosis phenomena, within cornea/conjunctiva regions, with BAK localizations. Moreover, an important accumulation of BAKs was observed at the sclerocorneal junction where is located the trabecular meshwork, a crucial structure involved in aqueous humor outflow. Moreover, differential analysis was carried out to find disease state biomarkers in each ocular structure. Thus, MSI offers new insight in ocular therapeutic/pharmaceutical research, especially to improve the eye distribution understanding for any new drug candidate in order to assist studies on drug efficiency or toxicity in specific tissues targeted by eye diseases.