Molecular imaging in the eye

Abstract

Molecular imaging plays an increasingly powerful role in elucidating pathophysiological pathways, in advancing drug discovery and in deciphering developmental processes. Multiple modalities, including optical imaging, ultrasound, nuclear imaging, computed tomography and various techniques of MRI are now being used to obtain fundamental new insights at the cellular and molecular level, both in basic research, using animal models and in clinical studies. In permitting unique optical access, the eye is particularly well suited for molecular imaging, for example, transgenic mice in which the fractalkine receptor is rendered intrinsically fluorescent to allow for in vivo monitoring of myeloid immune cells within the retina and choroid by scanning laser ophthalmoscopy (SLO). Retinal cell apoptosis can be assessed by intravitreal injection of fluorescent-labelled annexin 5 in vivo using a similar SLO technique. Intravital microscopy also allows visualisation of CD11c-positive dendritic cells in transgenic mice expressing yellow-fluorescent protein in these immune cells. Adoptive transfer of fluorescent-labelled transgenic T-cells enables visualisation of infiltration by specific T-cells into various eye compartments. On the other hand, functional imaging can be provided by new MR methodologies: deuterium MRI and diffusion MRI analysis techniques permit dynamic studies of water movement in animal eyes. MRI also enables pharmacokinetic studies on ocular drug delivery and detects biomarkers for treatment efficacy in retinopathies. Undoubtedly, these and further molecular imaging techniques currently being developed will have a fundamental impact on experimental and clinical ophthalmology and thus on our understanding of eye disease and development of therapy in general.

In Vivo Imaging of a New Indocyanine Green Micelle Formulation in an Animal Model of Laser-Induced Choroidal Neovascularization

“…During recent years, in vivo imaging of rodents in experimental eye disease models by using the confocal scanning laser ophthalmoscopy (cSLO) has been applied increasingly. [24][25][26][27][28][29] For example, imaging of real-time retinal cell apoptosis 25 and laser-induced CNV has been reported. [30][31][32][33][34] The aim of the current study was to develop a new formulation of ICG with better chemical stability and modified Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783 fluorescence characteristics, and to test this molecule in vitro and in an animal model with in vivo and ex vivo correlations.…”

In vivo Imaging with a Fundus Camera in a Rat Model of Laser-Induced Choroidal Neovascularization

“…Early recognition of malfunction and direct visualization of pharmacodynamics may result in optimization of therapeutic strategies and better treatment outcomes. In ophthalmology, molecular imaging has already been successfully applied in several animal models, using both exogenous and endogenous fluorescent probes [3,4,13]. A key advantage of the fundus camera is the ability to visualize multiple fluorescent samples with different characteristics, pharmacokinetics and chosen absorption/excitation spectra.…”

“…To date a number of experimental rodent models have been extensively studied [1,2,3,4]. Noninvasive fundus imaging in rodent models of retinal pathology, such as age-related macular degeneration or diabetic retinopathy, has been subject to intense research effort, leading to a better understanding of human conditions [5,6].…”

Novel Retinal Imaging Technologies

“…The modalities for MI may include PAI, optical imaging, ultrasound, OCT, and fluorescence to obtain fundamental images at the cellular and molecular level. Biomarkers are important as imaging tools and targets, such as intrinsic imaging contrast in tissue, targeted injectable contrast agents, reporter gene imaging and cell labelling, antibody labelling, protein expression, enzyme activity, nanoparticles, and apoptosis [35].…”