Permeability of Retinal Pigment Epithelium: Effects of Permeant Molecular Weight and Lipophilicity
Abstract
PURPOSE: To determine the effects of solute molecular weight and lipophilicity on the permeability of a retinal pigment epithelium (RPE)-choroid preparation. METHODS: Fresh RPE-choroid specimens from bovine eyes were placed in diffusion chambers for permeability experiments with carboxyfluorescein, fluorescein isothiocyanate (FITC)-labeled dextrans with molecular masses from 4 to 80 kDa, and beta-blockers exhibiting a wide range of lipophilicity (atenolol, nadolol, pindolol, timolol, metoprolol, and betaxolol). Permeability experiments were performed both in the choroid-to-retina (inward) direction and in the retina-to-choroid (outward) direction. Carboxyfluorescein and FITC-dextrans were determined by fluorometry, and beta-blockers by HPLC. The transepithelial electrical resistance and potential difference were monitored during the experiments. RESULTS: Permeability of the fluorescent FITC-dextran probes through RPE-choroid decreased significantly with the increasing size of the probe. RPE-choroid was 35 times more permeable to carboxyfluorescein (376 Da) than to FITC-dextran 80 kDa. The permeabilities of lipophilic beta-blockers were up to 8 and 20 times higher than that of hydrophilic atenolol and carboxyfluorescein, respectively. The lag time of solute flux across the RPE-choroid increased with the molecular weight and lipophilicity. Compared with published data on isolated sclera, bovine RPE-choroid was 10 to 100 times less permeable to hydrophilic compounds and macromolecules. The permeability of lipophilic molecules in RPE-choroid was in the same range as in the sclera. CONCLUSIONS: RPE is a major barrier and may be the rate-limiting factor in the retinal delivery of hydrophilic drugs and macromolecules through the transscleral route. For lipophilic molecules, RPE-choroid, and sclera are approximately equal barriers.
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The blood-retinal barrier (BRB) may impede the diffusion of molecules from the systemic circulation to the retina.
“The blood–retinal barrier (BRB)—comprising the tight junctional complexes between retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB)—may also impede the diffusion of molecules from the systemic circulation to the retina.”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [229]
The outer BRB is highly selective, allowing hydrophilic and larger molecules to cross at a slower rate than their small, lipophilic counterparts.
“the outer BRB is also highly selective, allowing hydrophilic and larger molecules to cross at a slower rate than their small, lipophilic counterparts [229].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [229]
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Retracted
- Authors
- Pitka¨nen, L., Ranta, V.-P., Moilanen, H., & Urtti, A.
- Affiliations
- University of Eastern Finland (FI)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2005-02-01
- Volume
- 46
- Issue
- 2
- Pages
- 641
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- OpenAlex
- W2107476817
- Cited by
- 261
- References
- 38
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 12 · 2023: 17 · 2022: 23 · 2021: 9 · 2020: 16 · 2019: 17 · 2018: 19 · 2017: 14 · 2016: 12 · 2015: 9 · 2014: 15 · 2013: 8 · 2012: 10
- FWCI
- 8.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- retinal pigment epithelium, molecular weight, lipophilicity, beta-blockers, FITC-dextran, carboxyfluorescein, transscleral drug delivery, transepithelial electrical resistance, time delay, macromolecule transport
- MeSH terms
- Adrenergic beta-Antagonists, Animals, Cattle, Choroid, Chromatography, High Pressure Liquid, Dextrans, Diffusion, Electric Conductivity, Fluoresceins, Molecular Weight, Permeability, Pigment Epithelium of Eye, Sclera, Diffusion Chambers, Culture, Fluorophotometry, Drug Delivery Systems, Fluorescein-5-isothiocyanate, Electric Impedance
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