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. 2021 May 9;13(5):678. doi: 10.3390/pharmaceutics13050678

Table 1.

Summary of the different ocular barriers and their main functions.

Segment of the Eye Ocular Drug Barriers Main Functions
Anterior Static Cornea Allows passive transport of hydrophobic drugs and blocks transport of hydrophilic drugs.
Conjunctiva Formation of tear film, lipophilic affinity to drugs due to its paracellular spaces.
Blood Aqueous Barrier Limitation of ion and small solute diffusion and hydrophilic drugs. Regulation of aqueous humor secretion through ion transporters and gap junctions, connexin 43.
Efflux pumps (ABC proteins) Enhance or restrict transportation of substrates and drug bioavailability, including both hydrophilic and hydrophobic.
Dynamic Tear film, turnover, and drainage Mucous layer creates a hydrophilic gel layer clearing pathogens and restricting drug delivery, especially hydrophobic drugs. Production and flow of lacrimal fluid avoids the accumulation of drugs.
Conjunctival lymph and blood flow Maintain metabolic function and immune protection.
Aqueous humor Protects avascular structures of the anterior chamber and provides nutrition to maintain ocular homeostasis. Easy drug distribution pathway for the anterior segment.
Choroidal lymph and blood circulation Responsible for 85% of the eye’s perfusion and helps in drug clearance by decreasing the concentration of hydrophilic drugs.
Posterior Static Sclera Permeation dependent on chemical or structural properties. Allows a more rapidly hydrophilic permeation than hydrophobic.
Bruch’s membrane Helps in the prevention of hydrophilic compounds permeation.
Blood Retinal Barrier Regulates the passage of solutes to the subretinal space. Presents with hydrophilic permeation.
Efflux pumps Enhance or restrict transportation of substrates and drug bioavailability, including both hydrophilic and hydrophobic.
Dynamic Choroidal lymph and blood circulation Responsible for 85% of the eye’s perfusion and helps in drug clearance by decreasing the concentration of hydrophilic drugs.
Anterior and Posterior Metabolic Cytochrome P450 Metabolize substances by conjugation or oxidation to avoid drug accumulation. Or convert prodrugs into active drugs modifying the solubility, bioavailability, and concentration.
Enzymes: peptidases, esterases