Better understanding of the pathophysiology of the early stages of age-related maculopathy (ARM) may guide development of better treatments and/or preventions of age-related macular degeneration. Prominent clinical and histopathologic lesions of early ARM involve Bruch's membrane, a thin connective tissue between the choriocapillaris and the RPE. Unlike the case for late ARM, for which several risk factors have been identified, the only consistently identified risk factor for early ARM is advanced age. It is, therefore, important to understand how age-related changes in Bruch's membrane predispose some individuals for retinal dysfunction. A decreased transport capacity of Bruch's membrane, perhaps caused by lipid accumulation, has been postulated to be a critical early event in the pathogenesis of ARM. However, morphometric studies have not yet been successful in identifying those moieties responsible for limiting the transport capacity of Bruch's membrane. QFDE is a morphological technique that preserves extracellular matrix in exquisite detail and allows structures to be visualized that are not seen using conventional transmission electron microscopy (TEM) techniques. QFDE offers a technology that, in other connective tissues, has provided new insights into the transport characteristics of these tissues. Our goal is to combine the technique of quick-freeze/deep-etch (QFDE) morphology with bioengineering analytic methods to evaluate this hypothesis, using well-preserved eyes from normal human donors.
Our specific aims are (i) to use the methods of quick-freeze/deep-etch (QFDE) morphology and lipid histochemistry in conjunction with conventional electron microscopy methods to characterize quantitatively the earliest ultrastructural changes in Bruch's membrane associated with lipid deposition in 20-70 year old donor eyes; (ii) to combine these results with analytical bioengineering tools to evaluate the effects of age-related changes on transport properties of Bruch's membrane; and (iii) to use an in vitro model of fluid and lipid transport through extracellular matrix to validate the results of the analytical studies and characterize the impact of lipid accumulation on transport.
| Curcio, Christine A; Johnson, Mark; Rudolf, Martin et al. (2011) The oil spill in ageing Bruch membrane. Br J Ophthalmol 95:1638-45 |
| Cankova, Zdravka; Huang, Jiahn-Dar; Kruth, Howard S et al. (2011) Passage of low-density lipoproteins through Bruch's membrane and choroid. Exp Eye Res 93:947-55 |
| Curcio, Christine A; Johnson, Mark; Huang, Jiahn-Dar et al. (2010) Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration. J Lipid Res 51:451-67 |
| Curcio, Christine A; Johnson, Mark; Huang, Jiahn-Dar et al. (2009) Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins. Prog Retin Eye Res 28:393-422 |
| McCarty, William J; Chimento, Melissa F; Curcio, Christine A et al. (2008) Effects of particulates and lipids on the hydraulic conductivity of Matrigel. J Appl Physiol 105:621-8 |
| Huang, Jiahn-Dar; Curcio, Christine A; Johnson, Mark (2008) Morphometric analysis of lipoprotein-like particle accumulation in aging human macular Bruch's membrane. Invest Ophthalmol Vis Sci 49:2721-7 |
| Johnson, Mark; Dabholkar, Arun; Huang, Jiahn-Dar et al. (2007) Comparison of morphology of human macular and peripheral Bruch's membrane in older eyes. Curr Eye Res 32:791-9 |
| Huang, Jiahn-Dar; Presley, J Brett; Chimento, Melissa F et al. (2007) Age-related changes in human macular Bruch's membrane as seen by quick-freeze/deep-etch. Exp Eye Res 85:202-18 |
| McCarty, William J; Johnson, Mark (2007) The hydraulic conductivity of Matrigel. Biorheology 44:303-17 |
| Overby, Darryl R; Johnson, Mark (2005) Studies on depth-of-field effects in microscopy supported by numerical simulations. J Microsc 220:176-89 |
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