1. Static Barriers:
1. Cornea:
The cornea is the transparent outermost layer of the eye and acts as the primary barrier to the topical application of drugs.
Its unique three-layered structure – comprising the epithelium, stroma, and endothelium – provides challenges for drug penetration.
Lipophilic drugs often find it easier to penetrate the lipophilic epithelium but struggle with the hydrophilic stroma. Conversely, hydrophilic drugs can't easily pass through the epithelium.
2. Blood-Aqueous Barrier:
Formed by non-fenestrated capillaries of the ciliary processes and the tight junctions of the non-pigmented epithelium, this barrier limits drug entry into the aqueous humor from the blood.
3. Blood-Retinal Barrier (BRB):
It consists of two components:
Inner BRB: Formed by tight junctions between retinal capillary endothelial cells, it restricts the passage of large molecules and potential neurotoxins.
Outer BRB: Formed by retinal pigment epithelial cells (RPE), it regulates nutrient and metabolite transport between the choroid and the neural retina.
2. Dynamic Barriers:
1. Tear Turnover and Drainage:
Tears constantly wash away foreign particles, including topically applied drugs. The rapid turnover rate of tears can significantly reduce the residence time of the drug on the ocular surface.
2. Conjunctival Absorption:
Drugs applied topically can be absorbed into the systemic circulation via the conjunctival vessels, which reduces the amount of the drug available for ocular action.
3. Metabolic Enzymes:
The eye has a range of enzymes, particularly in the cornea, which can metabolize and degrade drugs, further reducing their bioavailability.
