Mouse models of age-related macular degeneration.

Lions Eye Institute, Centre for Ophthalmology and Visual Science, Department of Molecular Opthalmology, The University of Western Australia, 2 Verdun Street, Nedland Western Australia 6009, Australia.
Experimental Eye Research (Impact Factor: 3.02). 06/2006; 82(5):741-52. DOI: 10.1016/j.exer.2005.10.012
Source: PubMed

ABSTRACT Recent advances in genetic technologies have greatly accelerated our ability to find disease-related genes and to generate animal models. The availability of ocular tissues with known genetic diseases are greatly contributing to our understanding of retinal disease processes including age-related macular degeneration (AMD), and panretinal and cone degenerations. While the macula is a highly specialised area of the retina not present in many mammals, the use of animal models such as mouse strains will give basic physiology and visual processing genetics relevant to human AMD. This review aims to provide a framework for better understanding some of the existing animal models and the knowledge that has been derived from their evaluations.

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    ABSTRACT: Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide in the elderly population. Optometrists, as primary eye health care providers, require the skills and knowledge to accurately diagnose and manage AMD patients. There is an overwhelming body of research related to the clinical presentation, etiology, epidemiology, and pathology of this disease. Additionally, the evolution of new imaging modalities creates new opportunities to clinically detect and analyze previously uncharacterized and earlier changes in the retina. The challenge for optometrists is to combine all this information into an applicable knowledge base for use in everyday clinical assessment of AMD so that timely and accurate referrals can be made to retinal specialists. This review attempts to address this issue by linking the clinical presentation of AMD with the underlying disease biology. We emphasize the contribution of recent noninvasive imaging technologies to the clinical assessment of early and more advanced AMD including optical coherence tomography, fundus autofluorescence, and infrared reflectance.
    Optometry and vision science: official publication of the American Academy of Optometry 05/2014; · 1.53 Impact Factor
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    ABSTRACT: Indocyanine Green Angiography (or ICGA) is a technique performed by ophthalmologists to diagnose abnormalities of the choroidal and retinal vasculature of various eye diseases such as age-related macular degeneration (AMD). ICGA is especially useful to image the posterior choroidal vasculature of the eye due to its capability of penetrating through the pigmented layer with its infrared spectrum. ICGA time course can be divided into early, middle, and late phases. The three phases provide valuable information on the pathology of eye problems. Although time-course ICGA by intravenous (IV) injection is widely used in the clinic for the diagnosis and management of choroid problems, ICGA by intraperitoneal injection (IP) is commonly used in animal research. Here we demonstrated the technique to obtain high-resolution ICGA time-course images in mice by tail-vein injection and confocal scanning laser ophthalmoscopy. We used this technique to image the choroidal lesions in a mouse model of age-related macular degeneration. Although it is much easier to introduce ICG to the mouse vasculature by IP, our data indicate that it is difficult to obtain reproducible ICGA time course images by IP-ICGA. In contrast, ICGA via tail vein injection provides high quality ICGA time-course images comparable to human studies. In addition, we showed that ICGA performed on albino mice gives clearer pictures of choroidal vessels than that performed on pigmented mice. We suggest that time-course IV-ICGA should become a standard practice in AMD research based on animal models.
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    ABSTRACT: Purpose: Oxidative stress in the retinal pigment epithelium (RPE) is a contributing factor to age related macular degeneration (AMD). To develop a mouse model of mitochondrial oxidative stress, we used a conditional knockout of the Sod2 gene (encoding manganese superoxide dismutase) in the RPE. Methods: Mice, in which exon 3 of Sod2 was flanked by loxP sites, were transgenic for PVMD2-rtTA and tetO-PhCMV cre, so that cre recombinase was expressed only in the RPE after doxycycline (dox) treatment. Controls included mice not treated with dox and dox-treated Sod2flox/flox mice lacking cre. Mice were followed over a period of nine months by spectral domain optical coherence tomography (SD-OCT), digital fundus imaging and electoretinography (ERG). Following sacrifice, retinas were examined by microscopy or by immunohistochemistry. Contour length of rod outer segments and thickness of the RPE layer were measured by unbiased stereology. Results: Following dox-induction of cre, Sod2flox/flox cre mice demonstrated increased oxidative stress autofluorescent material in the RPE. They showed a decline in the ERG response and thinning of the ONL that were statistically significant by siax months. At this time, the choroid appeared distended. Fundus micrographs displayed pigmentary and vascular abnormalities. By nine months following deletion of Sod2 mice, the RPE was thicker the rod outer segments were significantly longer over most of the retina, though localized atrophy of photoreceptors was apparent in some eyes. Conclusions: Tissue-specific reduction in MnSOD induced oxidative stress leading to RPE dysfunction and death of photoreceptor cells and injury to Bruch's membrane and the choroid.
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