Ophthalmology Research

We are investigating the ability of specific oxidative catalysts to modulate the scarring of a wound after a filtering procedure. We are attempting to see if a surgical sponge with these oxidative catalysts attached will keep a wound open by blocking fibrosis. The purpose of this research is to develop a method to block fibrosis so that an access channel for aqueous humor can be produced in cases of glaucoma that do not respond to other treatment modalities. At the moment, we have found that this material will block fibrosis in a rabbit eye. Future studies will involve covalently attaching the oxidative catalyst to a Molteno valve so the catalyst is permanently located at the site where the unwanted scar formation occurs.

Ted W. Reid, PhD

Our collaborative drug design research program involves a combination of three different methods: 1) NMR spectroscopy and computer-assisted modeling used to determine the solution structure of substance P (SP) and new analogs and their interaction with the SP receptor; 2) organic synthesis techniques used to make new amino acids which will then be incorporated into new SP analogs based on modeling studies and the results of physiological assays; 3) different physiological and biological assays used to determine how the new SP analogs can interact with the SP receptor. Recent results show that small changes in the stereochemistry of SP around a single bond can be detected by the SP receptor and that these stereospecific changes can be used to detect different classes of SP receptors. One of these new compounds has been shown to stimulate a response at 1/10 the concentration necessary for SP. Based upon this information, we are now synthesizing a new molecule where the essential groups are locked into a specific orientation. Our long-term goal is to produce a SP molecule that is stable in a physiological environment and yet will readily activate a specific SP receptor.

Ted W. Reid PhD
David Birney PhD
Robert Walkup PhD
Li Xiang PhD

Pterygia are abnormal growths on the surface of the eye and are a common worldwide ophthalmologic problem in which vision may be impaired by the growth of tissue from the limbal region of the conjunctiva across the cornea. We have previously shown that pterygia result from an abnormal limbal epithelial stem cell that overexpresses p53 gene product probably due to a UV induced mutation in that gene. The current aim of this project is to determine whether metalloproteinases play a role in the ability of the mutated limbal stem cells to migrate onto and dissolve Bowman's layer and whether that role is different in limbal tumors.

Ted W. Reid, PhD
Nicholas Dushku, MD

 

2007    Young, Rockefeller S.L., Kenn A. Freedman. "The Pupil: Physiology and Function." 
Duane's Foundations of Clinical Ophthalmology Volume 2, Chapter 9. Ed. William Tasman, MD and Edward A. Jaegar, MD. Philadelphia: Lippincott Williams & Wilkins, 2007. 

 http://duanessolution.com 

Kenn Freedman, MD
Rockefeller Young, PhD

 

We have recently shown that the covalent attachment of selenium to a solid matrix will result in a biomaterial that will inactivate growth factors and block cellular growth. In particular, we have shown that we can inhibit the growth of lens epithelial cells. In collaboration with Dr. Stephen Kosto of Advanced Plasma Systems (St. Petersberg, Fl.) we have developed a technique to produce attachment sites on the surface of an intraocular lens (IOL). Using these treated lenses, we are covalently attaching selenium to an IOL to see if it will inhibit secondary cataract formation in a rabbit.

Ted W. Reid, PhD

Julian Spallholz, Ph.D.
Wade Graham, M.D.
David L. McCartney, MD

This research focuses on the mechanism by which peptides interact with cellular receptors to stimulate physiological events. One peptide currently under investigation is the neuropeptide substance P (SP). SP is eleven amino acids long and has been extensively studied by non-ocular scientists because of its many general physiological effects (smooth muscle contraction, inflammation, neurotransmission, blood vessel dilation, histamine release, and activation of the immune system). Studies in our lab have recently found that SP will stimulate epithelial cell growth and modulate the attachment of epithelial cells to their underlying matrix. Additional information implicates a key role for SP in healing ulcers. Studies on SP are investigating its potential to modify the attachment of epithelial cells to a cornea after wound healing. We are looking at both the strength of the attachment and the ultrastructure of the cornea after wounding followed by treatment with SP. This study is based on our findings that SP plays an important role in cellular attachment for epithelial cells and thus is probably the underlying cause of neurotrophic ulcers. Additionally, we are synthesizing new and novel analogs of SP in our Ocular Drug Design Center which will be tested in our model systems. We have recently produced an SP analog that has 10 times the activity of SP.

Ted W. Reid PhD
David Birney PhD
Robert Walkup PhD
Li Xiang PhD