The rabbit as an animal model for post-natal vitreous matrix differentiation and degeneration

Los, Leonoor I.

doi:10.1038/eye.2008.39

Cited by 39 publications

(24 citation statements)

References 24 publications

(37 reference statements)

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“…7) and that these changes were similar to those induced by trypsin (Figs. 5,8). Global effects of plasmin on the vitreous body outside the vitreoretinal interface have been reported elsewhere.…”

Section: Discussionmentioning

confidence: 80%

“…To better understand the higher-level organization of the vitreous, alternative techniques have been used. For example, in aged human vitreous, injected colored dyes have highlighted fluid-filled lacunae, 8 and slit beam illumination has Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783 indicated collapsed and tortuous fibers. [9][10][11] Noninvasive ultrasound 12,13 and magnetic resonance-based 14,15 techniques also have proved useful in assessing age-related vitreous liquefaction, but are currently limited by low spatial resolution.…”

mentioning

confidence: 99%

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Quantitative Imaging of Enzymatic Vitreolysis-Induced Fiber Remodeling

Filas

Shah

Zhang

et al. 2014

Investigative Ophthalmology & Visual Science

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Proteoglycan loss due to enzymatic vitreolysis differentially increases fiber alignment at locations where tractions are most common. We hypothesize that a similar mechanism leads to retinal complications during age-related vitreous degeneration. Structural changes to the entire vitreous body (as opposed to the vitreoretinal interface alone) should be evaluated during preclinical testing of pharmacological vitreolysis candidates.

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Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 99%

Quantitative Imaging of Enzymatic Vitreolysis-Induced Fiber Remodeling

Filas

Shah

Zhang

et al. 2014

Investigative Ophthalmology & Visual Science

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“…3, Table 2). Furthermore, Los (2008) showed that aging rabbit eye may be a good model for human vitreous liquefaction based on anatomical and histological analysis. Such a model may be a better approach than enzyme treatments to investigate the effect of the liquefying matrix or vitrectomy on vitreal drug elimination.…”

Section: Rabbit As An Animal Model In Intravitreal Pharmacokineticsmentioning

confidence: 99%

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Amo

Urtti

2015

Experimental Eye Research

182

136

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Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics.

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“…Despite this, some data obtained in rabbits can be useful to understand the mechanisms of ocular drug delivery such as the location and distribution of Galbumin™ in the eye after iontophoresis application and the pathway of Galbumin™ clearance after intravitreal injection. At the anatomical and histological levels, human and rabbit vitreous matrices are sufficiently similar to make the rabbit a promising animal model for the study of vitreous matrix differentiation and degeneration (Los, 2008). In summary, caution should be exercised to utilize the present results in ocular delivery development.…”

Section: Discussionmentioning

confidence: 99%

Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI

Molokhia

Jeong

Higuchi

et al. 2009

Experimental Eye Research

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The distribution and clearance of macromolecules in ocular delivery are not well understood. It has been hypothesized that iontophoresis can enhance transscleral delivery of macromolecules. The objective of this study was to investigate the ocular distribution of a macromolecule after transscleral iontophoretic delivery and intravitreal injection in vivo using nuclear magnetic resonance imaging (MRI) and to compare these results. Experiments of constant current transscleral iontophoresis of 4 mA or intravitreal injection were performed on New Zealand white rabbits in vivo. Iontophoresis experiments were also performed on rabbits postmortem. Galbumin™ (Gd-labeled albumin) was the model permeant surrogate to clinical therapeutic agents. MRI was used to monitor the distribution of the molecule in the eye after ocular iontophoresis and intravitreal injection. In addition, the conjunctiva, sclera, choroid, and retina were extracted in the transscleral iontophoresis study to determine the amounts of Galbumin™ in these tissues using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The results show that iontophoresis enhanced the ocular delivery of Galbumin™. The macromolecule was mainly delivered into the conjunctiva and sclera in microgram quantities and then diffused towards the posterior section in the upper hemisphere of the eye in vivo. Both in vivo and postmortem studies show that the iontophoretic delivery of Galbumin™ into the vitreous was below the detection limit. In the intravitreal injection study, the diffusion coefficient of Galbumin™ in the vitreous humor was estimated to be close to that of free aqueous diffusion.

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The rabbit as an animal model for post-natal vitreous matrix differentiation and degeneration

Cited by 39 publications

References 24 publications

Quantitative Imaging of Enzymatic Vitreolysis-Induced Fiber Remodeling

Quantitative Imaging of Enzymatic Vitreolysis-Induced Fiber Remodeling

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data

Transscleral iontophoretic and intravitreal delivery of a macromolecule: Study of ocular distribution in vivo and postmortem with MRI

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