Thomas T. Norton - US grants

Understanding the relationship between neuronal morphology and the function of visual system neurons is an important step in understanding the neural mechanisms of visual function. We propose three experiments using intracellular (horseradish peroxidase) labeling of physiologically identified neurons to explore this relationship in the tree shrew. This animal has well-developed geniculostriate and extrastriate visual pathways, both capable of mediating form vision. Thus it provides a excellent model to investigate the relationship between the receptive-field properties of neurons and the form vision mediated by these properties in the two separate afferent pathways. 1) In the extrastriate pathway, we will determine, at the level of the superior colliculus, whether the five functional cell classes identified by Albano et al. (1978) are related to the distinct morphological classes of cells seen in Golgi studies. Additionally, we will determine whether any or all of these physiologically-identified cell classes have locally ramifying axon-like processes which may contribute to circuitry within the superior colliculus. 2) In the geniculostriate pathway, at the level of the LGN, we will determine whether W-, X- and T-like cells have the same morphological characteristics as W-, X- and Y-cells in cat. Anatomical and physiological studies in tree shrew suggest, alternatively, that morphological characteristics may be more closely related to whether the cells are ON-center of OFF-center. 3) In the striate cortex we will determine whether parallel ON and OFF channels are present from the retina through the striate cortex in tree shrew by examining whether neurons responsive to light ON and light OFF are segregated into different subregions of layer IV. In addition, we will examine the destination of the locally projecting axons of these cells to determine whether ON and OFF pathways continue beyond the first synapse in cortex.

The goal of this project is to understand the "emmetropization" mechanism that uses visual signals to match the axial length of juvenile eyes to their optical power. Normally this mechanism produces eyes with little refractive error. However, a significant proportion of the population develops refractive errors, particularly myopia, in which the eye is too long for its own optical power. In high myopia, the axial elongation (which is not corrected by optical treatments, including refractive surgery) is a risk factor for glaucoma and retinal detachment, making myopia the 7th leading cause of blindness in the U.S. The emmetropization mechanism has at least three key components: 1) the retina, which detects the amount of defocus, 2) a signaling cascade from the retina, through the choroid to the sclera (the fibrous outer coat of the eye), and 3) fibroblasts in the sclera which respond to retinal signals by regulating the axial length. Our hypothesis is that remodeling of the scleral extracellular matrix controls scleral extensibility, axial elongation and refractive state. In the previous project period, a pattern of changes in mRNA levels was found for specific proteins in tree shrew sclera during the development of myopia induced with monocular form deprivation (MD) and during recovery from induced myopia. In the proposed project period we will expand on this discovery. Specific Aim 1 will examine whether myopia induced with a minus-power lens produces the same pattern of changes in scleral mRNA levels (with a different time-course) as when form deprivation is used. Specific Aim 2 will examine the role played by specific proteins in regulating scleral remodeling. We will measure changes in mRNA and protein levels of a membrane-bound matrix metalloproteinase (MT1- MMP), of MMP-3 and mRNA levels of proteoglycan core proteins (biglycan, aggrecan, lumican and fibromodulin) during the development of minus-lens induced myopia and recovery. Specific Aim 3 will examine the potential role of all-trans-retinoic acid (at-RA) in the signaling cascade to the sclera. We will measure changes in specific mRNAs and changes in scleral extensibility (creep rate) induced in organ culture by physiological levels of at-RA. These experiments will expand our understanding of the visual regulation of axial length and refractive state by describing the molecular events that occur in the sclera of eyes developing myopia. Under- standing the mechanisms regulating scleral remodeling may point the way toward targets for drug intervention to one day control myopia progression.

This application is for continued core support of a Vision Science Research Center located in the School of Optometry, University of Alabama in Birmingham. The requested funds would provide support personnel, equipment, and supplies for five research support modules shared by a group of twenty-one vision scientists. The support modules are I-Center Administration, II-Electronics, III-Tissue Processing Module, IV-Data Management and Analysis (Computer), and V-Illustration and Graphics. Fourteen of the participants in the center have faculty appointments in either the Department of Physiological Optics or the Department of Optometry, both in the School of Optometry. The remaining seven participants have faculty appointments in either the Departments of Anatomy, Chemistry, Pharmacology, Physiology, or Psychology. The center is an administrative subunit of the Department of Physiological Optics and the Center Director, along with the four Module Directors, are responsible for the administration of the Center's activities. The major research focus of the center is neurobiology, with almost half of the Center's participants actively involved in anatomical, physiological, and psychophysical studies of the visual system. Other areas of emphasis are corneal biochemistry and physiology, ocular pharmacology, photochemistry, epidemiology of refractive error, and visual optics. In addition to the existing CORE support, the continued development and growth of the Vision Research Center is supported by faculty salaries from the various departments involved, and by research support services, equipment and facilities provided by individual departments and the university as a whole. The continued CORE support requested in this application provides shared resources not available through other funding mechanisms. These shared facilities increase the efficiency and productivity of research efforts on individually funded projects, afford participants more flexibility in taking new research directions, and promote more collaborative research among a group having multidisciplinary approaches to vision science.

biomedical equipment purchase;

vision; biomedical equipment resource; biomedical facility; biomedical equipment development;