Studies of corneal structure and transparency

This thesis presents the results and conclusions of experiments designed to extend the current models for the origin of corneal transparency. The cornea is the transparent window at the front of the eye, which is responsible not only for the majority of refraction of light that enters, but also the protection against damage, infection and mechanical stress. The property of transparency is only realised by corneal and lens tissue in the human body. In the cornea, it has long been suspected to be caused by the precise arrangement of the fibrils of collagen that are contained within the central layer, the stroma, regulated by the sulphated proteoglycans (PG) that keep fibril spacing within acceptable boundaries. These models are consistent and give a complete description of the reasons for the transparency of a stroma that is entirely acellular. However, it is well known that the stroma is not acellular, and that the short-range order that is critical for transparency would necessarily be disturbed by the cells of the stroma, the keratocytes, which are at least an order of magnitude thicker than the maximum allowed range. Originally, an acellular stroma was considered to be a reasonable approximation due to the perceived sparsity of the cells, but more recent measurements have cast doubt upon this, and explanations have begun to focus on the properties of the cells themselves. One such property would be their refractive index (RI). If the cells could match their own RI to that of their surroundings then they would not scatter and hence would not cause a loss in transparency. This research attempts to measure that RI and by comparison with previously calculated values for the RI of the extra-cellular matrix, attempts to quantify the scale of the scattering that any mismatch would cause, using theoretical models based on both Mie scattering and finite-difference time-domain methods. In addition to models of healthy corneas, this thesis also provides results and conclusions drawn from studies of pathological corneas and discussions of how the pathology, and the treatments, can cause initial losses in transparency. The first such study concerned a cornea afflicted with keratoconus, a disorder of as yet unknown origin that causes the weakening of the corneal tissue, leading to a characteristic cone-shaped cornea, which had been treated with a full penetrating keratoplasty (PK) transplant before being donated. The study was conducted using the techniques of electron microscopy and x-ray diffraction, to both qualitatively and quantitatively analyse the properties of the fibrils and their spacing. This was done on both the original sections of diseased tissue and the donated sections, in order to investigate the idea of keratoconus recurring in previously healthy donated tissue. Any such discovery could provide evidence that keratoconus is not an entirely inherited disorder. The structural properties of the observed scar, that was present as a direct result of the PK procedure that was carried out decades before, were also investigated using the same methods. This investigation was designed to provide insights into the priorities of wound healing in the cornea, and whether any appreciable change in fibril spacing could account for the observed loss of transparency. The final study presented here is a novel tomographic reconstruction of a feature of the disease macular corneal dystrophy (MCD). MCD is a genetic disorder that affects the sulphation of the PG keratan sulphate. MCD gives rise to a multitude of abnormalities but one that has not been fully investigated is the apparent presence of areas within the stroma entirely populated by PGs, with no collagen present. This study attempts to reconstruct three-dimensional views of these lakes, as well as stromal lamellae, in order to investigate the interactions between free PGs and between PGs and collagen in MCD

Psr1p interacts with SUN/sad1p and EB1/mal3p to establish the bipolar spindle

Regular Abstracts - Sunday Poster Presentations: no. 382During mitosis, interpolar microtubules from two spindle pole bodies (SPBs) interdigitate to create an antiparallel microtubule array for accommodating numerous regulatory proteins. Among these proteins, the kinesin-5 cut7p/Eg5 is the key player responsible for sliding apart antiparallel microtubules and thus helps in establishing the bipolar spindle. At the onset of mitosis, two SPBs are adjacent to one another with most microtubules running nearly parallel toward the nuclear envelope, creating an unfavorable microtubule configuration for the kinesin-5 kinesins. Therefore, how the cell organizes the antiparallel microtubule array in the first place at mitotic onset remains enigmatic. Here, we show that a novel protein psrp1p localizes to the SPB and plays a key role in organizing the antiparallel microtubule array. The absence of psr1+ leads to a transient monopolar spindle and massive chromosome loss. Further functional characterization demonstrates that psr1p is recruited to the SPB through interaction with the conserved SUN protein sad1p and that psr1p physically interacts with the conserved microtubule plus tip protein mal3p/EB1. These results suggest a model that psr1p serves as a linking protein between sad1p/SUN and mal3p/EB1 to allow microtubule plus ends to be coupled to the SPBs for organization of an antiparallel microtubule array. Thus, we conclude that psr1p is involved in organizing the antiparallel microtubule array in the first place at mitosis onset by interaction with SUN/sad1p and EB1/mal3p, thereby establishing the bipolar spindle.postprin

Optic Nerve Deformation by Eye Movements

Ocular rotation can cause mechanical deformation of the optic nerve head and surrounding tissues. During extreme angles of gaze, the optic nerve can become stretched and impose strain on other ocular tissues. Over a lifetime, the ill effects of repetitive mechanical injury from large adduction can compound, resulting in progressive optic neuropathy in some glaucoma patients.We investigated the etiology of this form of glaucoma through a series of papers focusing on anatomical analysis of the human optic nerve from donated tissue and clinical studies utilizing optical coherence tomography (OCT) and confocal scanning laser ophthalmoscopy (cSLO). The optic nerve is surrounded and protected by a bi-layered dural sheath that bears the bulk of exerted mechanical force. Elastin fibers embedded within the sheath and peripapillary tissues around the nerve head form a three-dimensional meshwork that reinforces the tissue against mechanical strain. While the tissue at the globe optic nerve junction is heavily fortified with organized layers of collagen and elastin fibers, irregularities in the elastin fiber arrangement resulting in large dense elastin deposits were observed to correlate with older age. These elastin deposits could be a pathologic byproduct of optic nerve injury from mechanical strain, or serve as a protective mechanism to further reinforce the ocular tissues.In OCT studies, adduction of angles beyond 26� caused marked deformation of the peripapillary tissues around the optic nerve head, and choroidal volume change. cSLO imaging showed similar deformations of the retina surface during large angle adduction. Ocular tissue of younger subjects appears more compliant, while those of glaucoma patients were stiffer and thus experienced less deformation.We explored possible therapies for optic nerve traction during eye movement. Using collagen crosslinking to fortify ocular tissue, we observed that exposure to riboflavin and UV light can stiffen scleral tissue. In addition, we investigated whether prostaglandin agonists could be used to reduce ocular fat and found that topical administration of these agonists had insignificant effects on the retrobulbar fat

2006-2007 Undergraduate Catalog

Annual publication of degrees offered and their requirements for all undergraduate students enrolled at the University of Central Oklahoma

2010-2011 Undergraduate Catalog

Annual publication of degrees offered and their requirements for all undergraduate students enrolled at the University of Central Oklahoma