Organic cation transporter 1 in the lacrimal gland facilitates the entry of systemic drugs causing ocular surface toxicity.

Many of the daily systemic medications (parenteral and oral) used to treat various diseases are known to cause ocular toxicities - leading to vision loss. How these medications gain entry into the eye despite the ocular barriers is an important question to be addressed. Various reports show almost 30-40 % of systemic drugs causing ocular toxicity are organic cation in nature. We hypothesize these systemic drugs (cations) are non-specifically recognized as endogenous substrates by organic cation transporter (OCT1) in the lacrimal gland, thereby facilitating its entry into the anterior eye segment. Therefore, we studied the expression and localization of OCT1 in the lacrimal gland of rabbits. Further, to prove our hypothesis, OCT1 substrates (known as well as predicted from our previous Artificial Intelligence study) were administered intravenously in the presence and absence of topically administered OCT1 blockers. Our findings show, OCT1 gene and protein expression in the lacrimal gland, with its localization in the terminal acinar cells. The tear levels of intravenously administered substrates decreased in the presence of topical OCT1 blockers, indicating - a) the entry of systemic drugs into the eye via lacrimal secretion and b) OCT1 in the lacrimal gland is involved in the drug transport (substrates) from blood to the eye. Though the role of transporters in toxicity is well-known, the current study opens a new avenue for understanding the role of transporters in ocular toxicity.