Absorption of Toxicants from the Ocular Surface: Potential Applications in Toxicology

Abstract

In relation to the eye, the body can absorb substances from the ocular surface fluid (OSF) in a few ways: directly through the conjunctival sac, through the nasal mucosa as the fluid drains into the nose, or through ingestion. Regardless of the absorption method, fluid from the conjunctival sac should be used as a toxicological matrix, even though only small quantities are needed. Contemporary analytical techniques make it a suitable matrix for toxicological research. Analyzing small quantities of the matrix and nano-quantities of the analyte requires high-cost, sophisticated tools, which is particularly relevant in the high-throughput environment of new drug or cosmetics testing. Environmental toxicology also presents a challenge, as many pollutants can enter the system using the same ocular surface route. A review of the existing literature was conducted to assess potential applications in clinical and forensic toxicology related to the absorption of toxicants from the ocular surface. The selection of the studies used in this review aimed to identify new, more efficient, and cost-effective analytical technology and diagnostic methods.

Keywords: drug; eye; matrix; modeled tissue; ocular surface fluid; particle pollution; toxicants; toxicology.

Figure 1

This review focuses on the ocular blood supply and lymphatic drainage. Key structures relevant to this discussion are outlined in the accompanying figure. For instance, the eyelids and pre-extrinsic eye muscles are not included in this outline, and the term “conjunctiva” refers to both the palpebral and bulbar types. The terminology used in this figure aligns with the FIPAT’s International Anatomical Terminology (Terminologia Anatomica—Second Edition) [4,5]. Additionally, ocular surface fluid migrates across a concentration gradient, which can influence the presence of drugs in the ocular surface fluid (OSF), even if those drugs are not administered directly to the eye. (Figure made using BioRender, University of Rijeka, Croatia, https://www.biorender.com, accessed on 17 February 2025, and Microsoft^® PowerPoint^®, Microsoft 365, 64-bit version 16.0.17531.20140, University of Rijeka, Croatia).

Figure 2

PRISMA 2020 diagram showcasing our search in three levels.

Figure 3

Fornixes (pockets) of the conjunctival sac. (Figure made using BioRender, University of Rijeka, Croatia, https://www.biorender.com, accessed on 17 February 2025).

Figure 4

Schematic of a hypothetical pharmacokinetic model for drug metabolism using in vitro/in silico methods, including liver organoids/liver-on-a-chip. The development of liver organoids, organs-on-a-chip, and the least complex spheroids provides a platform for personalized medicine studies as well. Simulations of the gallbladder and urinary bladder are also shown. (Figure made using the BioRender account of the University of Rijeka, Croatia, https://www.biorender.com, accessed on 17 February 2025).