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Scientific Abstract
Pfizer Ophthalmics 2004 Fellows Award for Excellence in Glaucoma Research
“Comparative Ultrastructural Analysis of Human Fetal and Adult Trabecular Meshwork by Two-Photon Microscopy”
A study of the pathophysiologic mechanisms underlying congenital glaucoma necessitates a clear conceptual understanding of the normal development of the anterior chamber angle. Theories of normal development include apoptosis of mesenchymal tissue, structural cleavage with differential growth rates, and resorption with macrophage involvement. Ultrastructural analysis of trabecular meshwork, thus far limited to studies using light, scanning and transmission electron microscopy of histological cross sections taken from dissected tissue samples primarily in non-human mammals, has provided us with a basic understanding of the architecture of the angle and its development, but it is uncertain if the normal three-dimensional architecture of the trabecular meshwork is unaltered by these conventional methods of analysis. There is considerable variation in trabecular meshwork development across mammalian species, and the few studies performed on human fetal tissue raises questions as to how the development of the anterior chamber angle in human eyes differs from that in other mammals. Two-photon microscopy is a new technology useful in nondestructive analysis of tissue, which allows visualization of deeper structures with less risk of tissue photodamage compared to conventional confocal microscopy. Two-photon microscopy also has the inherent benefit of optical sectioning, allowing the construction of three-dimensional images of scanned structures while leaving them unaltered structurally. The objective of our study is to analyze human trabecular meshwork with two-photon microscopy in fetal and adult eyes in order to better understand normal anterior chamber angle development in humans, as compared to that in other mammals. Specifically, we intend to evaluate trabecular meshwork beam and intertrabecular space size and cellular count in these specimens, as well as the specific trabecular meshwork components known to be involved in outflow function, including collagen and phagocytes using immunolabeling methods. Moreover, in evaluating the possible role of apoptosis in human anterior chamber angle development, we will perform apoptosis assays on our tissue samples. This fellowship award will provide the necessary funding to support us in achieving these specific objectives. We believe that two-photon microscopy can be particularly advantageous in structural evaluation of human trabecular meshwork. By using this technology to study the development of the trabecular meshwork in human fetal and adult eyes for the first time, we hope to gain valuable insight into the pathophysiologic basis of congenital glaucoma.
