3. Unusual presentation of patient who lost vision suddenly from Optic Nerve Head Drusen.

Faculty Mentors: Dr. Keltner, Dr. Werner, Dr Choi

Patient will be studied by Adaptive Optics (AO), High Resolution OCT, MFERG, and standard ERG.
Description: This is a unique case of a patient who went blind suddenly at high altitude in 1969. Patient has for over 35 years had very constricted visual fields from the sudden blindness with optic nerve drusen. Patient will have AO, High Resolution OCT, MFERG and Standard ERG, and Visual Fields done to define the status of his photoreceptors 35 years later. This is a unique case.

Length: Short Detailed case report

References:
1. Optic Disk Drusen, by Auw-Haedrich, Staubach, and Witschel, Survey of Ophthamology, Vol 47, Page 515-532, 2002
2. Liang J, Williams DR, Miller DT. Supernormal vision and high resolution retinal imaging through adaptive optics. J Opt Soc Am A. 1997; 14: 2884-2892.
3.Roorda A. Adaptive optics ophthalmoscopy. J Ref Surgery. 2000;16:S602-607.
4.Doble N. High resolution, in vivo retinal imaging using adaptive optics and its future role in ophthalmology. Expert Review of Medical Devices 2005;2:205-216.

4. Physician Interventions to Increase Patient Adherence (Compliance) to Glaucoma Medication Treatment

Mentor: Michele C. Lim, M.D.

Duration: Long Term

Description:
There are three specific aims:
1. Patient-physician communication - To investigate the effect of improved patient-physician communication on medication adherence.
2. Psychosocial aspects of medication adherence - To investigate the relationship between psychosocial factors and adherence.
3. Medication dosing - To investigate dosing frequency as well
as the use of multiple medications and its effect on adherence.

Reading List
Kass MA, Meltzer DW, Gordon M, Cooper D, Goldberg J. Compliance with topical pilocarpine treatment. Am J Ophthalmol 1986; 101:515-23.
Taylor SA, Galbraith SM, Mills RP. Causes of non-compliance with drug regimens in glaucoma patients: a qualitative study. J Ocul Pharmacol Ther 2002; 18:401-9.
Norell SE. Improving medication compliance: a randomised clinical trial. Br Med J 1979

5. Long Term Outcomes of Glaucoma Surgery in Patients with Aniridia

Mentors: Michele C. Lim, M.D., James D. Brandt, M.D.

Duration: Long Term

Descriptio:
This project is a retrospective review investigating the outcome of glaucoma surgery in patients with aniridia, a condition characterized by a rudimentary iris. Main outcome measures are intraocular pressure control and vision.

Reading List
Chandler and Grant's Glaucoma. Fourth edition. Page 629-631
Arroyave CP, Scott IU, Gedde SJ, Parrish RK 2nd, Feuer WJ. Use of glaucoma drainage devices in the management of glaucoma associated with aniridia. Am J Ophthalmol. 2003 Feb;135(2):155-9.
Swanner JC, Walton DS, Chen TC. Prevention of aniridic glaucoma with goniosurgery. Int Ophthalmol Clin. 2004 Winter;44(1):67-71.

7. Matrix Metalloproteases: Regulators of Corneal Clarity Following Injury.

Faculty Mentor: Dr. Rosenblatt

Description: During wound healing, the corneal produces an array of molecules which regulate corneal clarity. A group of proteases, known as matrix metalloproteases (MMPs), is responsible for controlling the remodeling of the collagen matrix and the production of scarring. More recently, these same molecules have been implicated in regulating angiogenesis. We are studying one such protease, MMP-7, which appears to act both as an anti-angiogenic and anti-scarring molecule in the cornea. Students working on this project will use a model of excimer laser wounding of transgenic mice deficient in MMP-7 expression to dissect the mechanisms of MMP-7's maintenance of corneal clarity.

Duration: Long Term

References:
Kure T, Chang JH, Kato T, Hernandez-Quintela E, Ye H, Lu PC, Matrisian LM, Gatinel D, Shapiro S, Gosheh F, Azar DT. Corneal neovascularization after excimer keratectomy wounds in matrilysin-deficient mice. Invest Ophthalmol Vis Sci. 2003 Jan;44(1):137-44.
Chang JH, Javier JA, Chang GY, Oliveira HB, Azar DT. Functional characterization of neostatins, the MMP-derived, enzymatic cleavage products of type XVIII collagen. FEBS Lett. 2005 Jul 4;579(17):3601-6.

9. Silk as a matrix for cellular growth

Faculty Mentor: Ivan R. Schwab M.D.

Description: Bioengineered tissue requires ex-vivo expansion of cellular elements but also requires a matrix protein or substrate to effectively allow the growth of these cells for eventual transplantation. We will explore silk as a matrix to grow fibroblasts and epithelial cells to create a 3-D matrix for transplantation back to the eye or other bodily organ. This is a new substrate, but little is known about its capabilities. There will be more than reading required. The needs will include a polymer chemist and the mentor can assist with this. The student will learn to grow epithelial cells, fibroblasts, and the immunofluorescence techniques for cellular staining. This could be a short project of about 1-3 months, but this would probably not result in a publication, or it is a year to several year project that could result in very exciting information. Like all research, though this is speculative, and the student must realize this. Although it has very exciting and creative potential, it remains speculative with a long road to success. The mentor has preliminary data to suggest that this may be a significant alternative to current substrates.

Duration: Can be short or long Term

References:
1. Altman GH, Diaz F, Jakuba C, et al: Sild-based biomaterials. Biomaterials 2003; 24: 401-6.
2. Nazarov R, Jin, HJ, Kaplan DL: Porous 3-D Scaffolds from regenerated silk fibroin. Biomacromolecules 2004; 5: 718-726.
3. Kim UJ, Park J, Kim HJ et al: Three-dimensional aqueous-derived biomaterial scaffolds from silk fibroin. Biomaterials 2005; 26 2775-85
4. Jin HJ & Kaplan DL: Mechanism of silk processing in insects and spiders. Nature 2003; 424: 1057-61.
5. Rahaman MN & Mao JJ: Stem cell-based composite tissue constructs for regenerative medicine. Biotechnology and Bioengineering 2005; 91: 262-84.

10. Analysis of dinoflagellates for Pax-6.

Mentor: Ivan R. Schwab

Description: Dinoflagellates are single celled organisms better known as plankton. A few species have subcellular eyes. It is not known whether these have Pax-6 or not. Pax-6 is the master gene for making eyes and is present in all sighted metazoan, and many non-sighted metazoan. This is an evolutionary pivot and would be important to determine if the protists had this gene or not. This helps determine if the protists radiated directly to the metazoan or if there was an earlier common stem organism. Similarly, it is not known if this animal has similar opsins as the metazoans-another key branching question. The preceptor MAY have access to these creatures and this will require advance notice. This would be done in cooperation with a scientist at Scripps Institute and may require some travel. But, if these can be found, the mentor can assist the student to do the science of this analysis for Pax-6. This is probably a year project, and would result in one or more publications.

Duration: Long Term

References:
1. Kreimer G Reflective properties of different eyespot types in dinoflagellates. Protist: 1999; 150: 311-23.
2. Pennisi E. Evolution of developmental diversity. Evo-devo devotees eye ocular origins and more. Science 2002; 296:1010-1.
3. Greuet C: Ultrastructural organization of the ocelloide of Nematodinium. Phylogenetic aspect of the evolution of Warnowiidae Lindemann dinoflagellates photoreceptor. Cytobiologie. 1978; 17: 114-36 (in French unfortunately).
4. Francis D. On the eyespot of the dinoflagellate, Nematodinium. J Exp Biol 1967; 47: 495-501.
5. More literature available, but in books from 1927-consult Mentor.

11. Phylogeny of retinal vascularization.

Mentor: Ivan R. Schwab, M.D.

Description: All sighted mammals must have nutrition delivered to the inner retina, but there are at least eight different ways of doing this within the mammalian classes. This project can be as deep as the student wants to go with it. To begin with, a review of these systems to include the comparative histology of each system with a phylogeny of how this developed evolutionarily has never been published. We will have the specimens necessary to do this, and this is basically for reading and writing with little or no lab work but it will take reading and writing. A publication would be expected and quite readily obtained with persistence.

Part 2. If the student wishes to pursue this project further, we would perform fluorescein angiography on representative species of all forms of retinal vascularization to compare speed of delivery and the exact mechanics of delivery. For some species this has never been done, and will require help from the Vet school which will require organization on the mentor's part so some advance notification will be required. Resources are available. This is likely to produce a thesis quality manuscript and should be considered as possible PhD quality work. Similar works have resulted in the satisfaction of a PhD. This would probably require a year.

Duration: Long Term

References:
1. De Schaepdrijver L, Simoens P, Lauwers H, De Geest JP. Retinal vascular patterns in domestic animals. Research in Veterinary Science 1989; 47: 34-42.
2. Duke-Elder SS: System of Ophthalmology Vol 1. The Eye in Evolution. London H. Kimpton 1958; 476-484. There are other pages, but at this writing I do not have access to this volume. The student should browse this volume for similar pages.
3. Pettigrew JD: Flying Primates? Megabats have the advanced pathway from eye to midbrain. Science 1986; 231: 1304-06.
4. Bellhorn R: Reference unavailable at time of writing-consult Mentor.