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Comparative Analysis of Intravitreal Diffusion Patterns Across Ex Vivo Human and In Vivo/Ex Vivo Animal Models
Anfisa Ayalon1, Avigail Beryozkin1, Katherine A Davoli1
1Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Investigative Ophthalmology & Visual Science
|May 20, 2026
Summary
The vitreous acts as a size-dependent barrier, limiting the spread of larger molecules like fluorescein dextran. This barrier function impacts drug delivery and gene therapy effectiveness within the eye.
Area of Science:
- Ophthalmology
- Biomedical Engineering
- Drug Delivery
Background:
- The vitreous humor's barrier properties are crucial for ocular drug delivery.
- Understanding vitreous diffusion is key for developing effective treatments, including gene therapies.
Purpose of the Study:
- To investigate vitreous barrier function using varying molecular weight fluorescein dextran molecules.
- To assess the impact of injection site and plasmin pretreatment on dye distribution.
Main Methods:
- Studied distribution of five fluorescein dextran molecular weights (3 kDa to 2 MDa) in ex vivo pig eyes.
- Utilized temporal or nasal injections and plasmin pretreatment in ex vivo and in vivo pig and ex vivo human eyes.
Main Results:
- Smaller fluorescein dextran (3-40 kDa) diffused widely, while larger molecules (500 kDa-2 MDa) showed restricted distribution.
- Plasmin pretreatment enhanced 40-kDa dye spread but not 2-MDa dye.
- In human eyes, 2-MDa dye delineated a non-penetrated vitreous bursa.
Conclusions:
- A size-dependent relationship exists between molecule size and vitreous spread.
- The vitreous barrier influences treatment distribution, with potential for slow drug release from vitreous bursae.
