Ophthalmology Department - Joint Clinical Research Center

The Joint Clinical Research Center (JCRC), developed by the Massachusetts Eye and Ear Infirmary and the Schepens Eye Research Institute for the Department of Ophthalmology at Harvard Medical School, facilitates the development of innovative diagnostic, therapeutic and preventative strategies to more effectively address intractable visual disorders and blindness and trains new leaders in both the clinical and pre-clinical fields.

The Center promotes increased scientific collaboration among laboratory and clinical researchers and integrates translational, clinical and outcomes research, thus creating an intellectual synergy and an environment which accelerates scientific discovery into state-of-the art patient care for those suffering from eye disease.

Director

Kathryn Colby, MD, PhD

Staff

Debra Schaumberg, OD, MPH, ScD: Epidemiology/Biostatistics Consultant
Erin Peters: Clinical Coordinator
Amy Harrington: Administrative Assistant

Ophthalmology - Centers of Excellence: Key Projects

I. Gene Therapy of Ocular Tumors

• Gene Immunotherapy of Retinoblastoma,
  Bruce Ksander, PhD and Shizuo Mukai, MD
  This is a basic research project that is attempting to engineer a vaccine against retinoblastoma, a potentially life-threatening eye cancer in children. The project is currently testing the feasibility of modifying existing white blood cells to attack tumor cells.
• Evaluation of Antibody Response to p53 in Ocular Melanoma,
  Gilles Benichou, PhD, DSc; Kathleen Egan, MPH, ScD; and Evangelos Gragoudas, MD
  (see also uveal melanoma)
  This project will evaluate cell response to protein p53 during the course of cancer in patients with ocular melanoma. Normal p53 prevents the expansion of abnormal, tumor-growing cells while in cancer cells p53 function is impaired, leading to tumor formation. Mutations in the p53 gene are the most frequent gene alterations in human cancer and produce tumors with treatment resistance and high rates of metastasis. This project will determine whether patients with ocular melanoma exhibit mutated p53 and the correlation between the nature of anti-p53 antibody response and the course of their disease.
• Development of a New Mouse Model of Human Ocular Adnexal Tumors,
  Bruce Ksander, PhD
  This study is developing an animal model of tumors of the eyelid and orbit to advance the study of these conditions.
• Role of IGF-1 in Choroidal Melanoma,
  Evangelos Gragoudas, MD and Patricia D’Amore, PhD
  This study is determining if insulin-like growth factors play a role in the clinical characteristics of ocular melanoma.

II. Dry Eye Syndromes

• Gender and Dry Eye Syndromes,
  David Sullivan, PhD; M. Reza Dana, MD, MPH and Debra Schaumberg, OD, MPH, ScD
  This is an epidemiological study of dry eye involving the collection of questionnaire data about dry eye symptoms as well as clinical exams and measurements. This project will create a database that looks at gender and the prevalence of dry eye.
• Measurement of Tear Mucin Levels in Dry Eye and Allergic Conjunctivitis Patients,
  Ilene K. Gipson, PhD and M. Reza Dana, MD, MPH
  This project will test whether the levels of two mucins differ in two patient groups compared with the normal population. Results will provide a framework for future studies focused on the regulation of these genes in eye surface diseases. Data from these studies will provide a better, more complete understanding of the disease process in dry eye and allergic conjunctivitis.

III. Corneal Endothelial Function and Genetics

• Translational Studies of Human Corneal Endothelial Transplants,
  Nancy Joyce, PhD
  These investigators are trying to develop techniques to implant new corneal endothelial cells into postmortem eyes. The corneal endothelium is responsible for maintaining the clearness of the cornea. These cells stop working in disorders like Fuchs' dystrophy. By determining the parameters needed to allow the injected endothelial cells to "take", these investigators are laying the groundwork for potential new techniques to treat disorders of the corneal endothelium. Currently, these diseases can only be treated by corneal transplantation.
• Mitochondria in Fuchs Dystrophy
  Kathryn Colby, MD, PhD
  Fuchs' corneal dystrophy is a common cause of decreased vision and eye pain in older adults. Its cause is unknown and there are no effective treatments for this disease. The cells that malfunction in Fuchs' dystrophy (the "corneal endothelium") require tremendous amounts of energy to work properly. This study will determine whether abnormalities in the genes of the energy-producing systems (the "mitochondria") of the corneal endothelium occur in Fuchs' dystrophy. A better understanding of the causes of Fuchs' dystrophy will help us design better treatments for this common cause of vision loss in older adults.

IV. Other Corneal Disorders

• Analysis of Potential Enhancers of Retention of Keratoprosthesis,
  Claes Dohlman, MD and Ilene Gipson, PhD
  This project is uncovering biological factors that influence the stability of the keratoprosthesis, an artificial cornea developed by Dr. Dohlman.

V. Vision Rehabilitation of Patients with Vision Loss

• Tri-field Lens Correction for Binocular Tunnel Vision Patients,
  Eli Peli, OD and Eliot Berson, MD
  Using an optical device (tri-field prism glasses) developed by Dr. Peli, these investigators are attempting to enlarge the very small functional visual field of patients with retinitis pigmentosa. The investigators hope that by enlarging the field of vision, the device will enable patients to have advanced mobility and quality of life.
• Reading from Electronic Displays-Bilateral Visual Impairment,
  Eli Peli, OD
  Reading is a major problem for many people with reduced vision. New technologies including electronic displays and computers offer alternative methods to view text. This project will examine how reading can be improved for patients with visual impairment of both eyes by using different display formats.

VI. Treatment of Retinal Disorders

• Photodynamic Therapy and RPE Lipofuscin,
  Francois Delori, PhD and Joan W.Miller, MD
  This study will explore how the application of photodynamic therapy, a new treatment modality for macular degeneration, changes the deposition of lipofuscin in cells underlying the retina, using a specialized instrument developed by Dr. Delori. This will aid in understanding the basic biology of what may become a far-reaching treatment for macular degeneration.
• Implantable Miniature Telescope,
  Kathryn Colby, MD and Joan Miller, MD
  This is a phase II-III study of the safety and efficacy of the implantable miniature telescope for patients with advanced age-related macular degeneration. Study subject enrollment is complete and follow-up in ongoing.

VII. Glaucoma Mechanisms

• Retinal Vascular Autoregulation in Normal Tension Glaucoma,
  Louis Pasquale, MD and J.W. McMeel, MD
  This study is exploring the hypothesis that normal tension glaucoma is associated with changes in the autoregulation of vascular tone, and therefore, blood flow in the retina.
• SDF-1 in Glaucoma,
  Cynthia Grosskreutz, MD, PhD and Diane Darland, PhD
  This study is determining if the growth factor SDF-1 (stromal-derived factor) is involved in the progression of glaucoma.

VIII. JCRC Sponsored Fellowship Program

Several years ago, the JCRC began a fellowship program to promote the training of promising clinician-scientists. Current JCRC clinical fellows are:

• Mitochondria in cultured endothelial cells from patients with Fuchs’ dystrophy.
  Patrick Yeh, MD (Faculty mentors: Kathryn Colby, MD and Nancy Joyce, PhD)
• Eliminating ocular tumors by Fas vesicle ligands
  Sean Koh, MD (Faculty mentors: Shizuo Mukai, MD and Bruce Ksander, PhD)
• Retroviral gene transfer for the regulatable expression of antiangiogenic metalloproteases in corneal epithelial cells
  Mark Rosenblatt, MD, PhD (Faculty mentors: Patricia D’Amore, PhD)

For more information about any of these studies or to refer a patient, please contact the Joint Clinical Research Center at 617-573-5537.

page updated: 1/17/07