Species variation in small molecule components of animal vitreous.

PURPOSE: We characterized differences in biochemical composition of the vitreous of different animal species with respect to small molecule constituents. METHODS: Vitreous samples were extracted from sheep, pig, Dutch Belted rabbits, and New Zealand white rabbits. The vitreous samples were investigated for acetylcholinesterase (AChE) activity and, in addition, were subjected to metabolomics determination using mass spectrometry. RESULTS: AChE activity varied across the species investigated with greater activity noted in larger animals. Principal component analysis demonstrated species differentiation in relation to metabolomic profile. Key peaks identified the importance of animal diet on small molecule composition of the vitreous. CONCLUSIONS: Our results highlighted principal and consistent differences in small molecule composition and enzymatic activity of the vitreous depending on species. Interesting differences were demonstrated, showing that diet potentially can impact on components of and metabolites contained within the vitreous. Material will be exchanged between vascular and retinal tissue with the vitreous compartment and as a nonvascular, slowly equilibrating "sink" might reflect changes in transporter activity. As a first step, understanding the differences in the metabolic profile of vitreous from different species may impact interpretation of such activity across different species.

A pharmacokinetic study of a combination of beta adrenoreceptor antagonists - in the isolated perfused ovine eye.

The treatment of posterior eye diseases, such as diabetic retinopathy and age-related macular degeneration, is of growing interest as the number of people affected by these conditions continues to rise. This study utilises the methods of cassette dosing and the perfused ovine eye model - to reduce animal usage and therefore animal time - to show that for a series of beta adrenoreceptor antagonists, lipophilicity is a key physicochemical property that governs drug distribution within the eye. Following intravitreal injection, lipophilic beta adrenoreceptor antagonists penetrate to the posterior eye, where they bind to the choroid and reside in the retina at greater concentrations than more hydrophilic beta adrenoreceptor antagonists, which preferentially penetrate to the anterior eye.

Effects of vitreous liquefaction on the intravitreal distribution of sodium fluorescein, fluorescein dextran, and fluorescent microparticles.

PURPOSE: The effects of vitreous liquefaction in the elderly on the distribution of drugs from intravitreal injections, depots, or devices remains unclear. The purpose of the present study was to develop a liquefied vitreous model that simulates the aged condition, to enable the study of clinically relevant drug distribution. METHODS: Dutch-belted rabbits were used to develop a study model using hyaluronidase as a vitreolytic agent. The effects of experimental vitreous liquefaction were investigated on intravitreal sodium fluorescein, fluorescein isothiocyanate-dextran (MW 150 kDa), and a suspension of 1-µm fluorescent particles. The distribution of these model compounds was monitored by retinal angiography with a confocal laser scanning system and ocular fluorophotometer. RESULTS: Hyaluronidase-treated vitreous humor (n = 6) was found to decrease the gel phase to 41% ± 9% (wt/wt; mean ± SD) compared with 81% ± 9% in the control eyes (n = 8; P < 0.05). The distribution of sodium fluorescein and fluorescein isothiocyanate dextran was greater in the liquefied vitreous than in the control. In comparison to the normal vitreous, fluorescent particles sedimented faster in the liquefied vitreous, and the distribution was more dispersed and scattered. CONCLUSIONS: A model of vitreous liquefaction in rabbits was successfully generated using intravitreal hyaluronidase. Small and large fluorescent molecules as well as particulates were distributed faster in liquefied vitreous than in the control. The results suggest enhanced convective flow and subsequent faster clearance in liquefied vitreous.

Intravitreal therapy for neovascular age-related macular degeneration and inter-individual variations in vitreous pharmacokinetics.

This article aims to provide an interpretation and perspective on current concepts and recent literature regarding the evidence for individualizing intravitreal therapy (IVT), particularly considering iatrogenic and patient factors in the management of neovascular age-related macular degeneration (AMD). As ocular parameters that govern IVT pharmacokinetics do vary between individuals with AMD, developing a personalized strategy could improve safety and efficacy. This has to be derived from clinical measurements and data from laboratory animals; however, it is recognized that the animal models used in the development of intraocular formulations differ in their vitreous geometry from humans. These factors may be of relevance to the design of ophthalmic formulations and optimizing treatment outcomes in AMD. Further studies are needed to drive improvements in clinical practice which are aimed at maximizing the efficacy profile in IVT for AMD by a more rigorous evaluation of patient and surgeon-related variables.