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Research & Discovery “Imagination is truly the key to any discovery, and science to cure blindness This Research & Discovery section highlights some of surgery, and; ocular therapeutics and surgery. Investiga- is no exception.It is the constant the many scientific contributions made in recent years tions have also expanded to include the specialty fields reexamination of the facts along with by the dedicated scientists in the HMS Department of of genomics, proteomics, gene-gene and gene-environ- Ophthalmology, whose investigations have resulted in ment interactions, gene therapies, and stem cell therapy. creative leaps of thought that give birth major advancements in medical science and ophthalmic HMS investigators also conduct preclinical investi- to innovation in every field.” practice. Discoveries made in various fields—includ- gations using a variety of disease models, and carry out ing genetics, immunology and ocular biology—have small-scale clinical trials to establish a foundation for — Michael Young, PhD, Associate Scientist, reshaped the foundations of ophthalmology and formed “first proof in man.” In recent years, this work has led Schepens Eye Research Institute many new paradigms for the repair, regeneration, and to revolutionary treatments for macular degeneration, rehabilitation of countless disorders. including the development of photodynamic therapy as Today, using a uniquely synergistic approach that well as a number of anti-angiogenesis agents. Current combines both laboratory research and applied medi- work focuses on the development of novel pharmaceu- cine, this pioneering team continues to advance clini- tical, biological, and gene-therapy approaches for the cal care for the eye. Fields under intensive study span treatment of blinding diseases. several areas: physiology, ocular inflammation and With ample collaborative dialogue between talented immunology, neoangiogenesis optic neuropathies; ocu- researchers and clinicians, scientific advances are being lar prostheses; new approaches to drug delivery; laser rapidly transformed into cutting-edge clinical practice. RETINA UVEA choroid ciliary iris macula pupil vitreous Illustration by Laurel Cook Lhowe CORNEA OPTIC NERVE/ GLAUCOMA lens 75 RESEARCH & DISCOVERY CORNEA CORNEA As the eye’s most powerful focusing struc- Because the inflammatory response The changing landscape of the molecular and physiological is a well-conserved host defense of atypical keratitis mechanisms that maintain corneal ture, the cornea is essential for acute vision. mechanism against injury or infec- Fungi and Acanthamoeba (a genus of transparency, as well as the patho- Injuries, infections, and genetic disor- tion, these studies are relevant to protozoa) are relatively uncommon logical processes that cause various insults to the eye beyond causes of corneal infections, yet corneal clouding. cornea ders can rob vision by disrupting normal EKC, and may lead to novel, ratio- both are difficult to treat and can corneal function. The HMS Department of nally designed therapies for numer- be visually devastating when they Laying the cornerstone of ous causes of corneal inflammation. occur. Kathryn Colby, MD, PhD, in corneal clarity research Ophthalmology houses the world’s largest collaboration with other colleagues How the corneal matrix maintains and most esteemed group of scientists and Treating herpes within HMS and nationwide, has its clarity is one of the fundamental keratopathy with the examined the changing landscape questions in ophthalmology, and physicians —nearly 80 MDs and PhDs in Boston KPro of these atypical pathogens, both at much of the current understanding all—committed not only to understanding Varicella zoster, the virus that causes Mass. Eye and Ear, and throughout of corneal clarity began with the the common childhood disease the United States. These studies early work of Claes Dohlman, MD, corneal biology, but also to treating or pre- known chickenpox, remains dor- demonstrated an increase in PhD. Using basic science approaches venting corneal disease. With a potent arse- mant in the nerves of most infected both fungal (Jurkunas, Behlau to analyze clinical samples, Dr. Dohl- individuals. However, the virus may and Colby, June 2009 issue of the man helped to define the molecular nal of tools, technologies, and knowledge, later reactivate and cause a painful journal Cornea), and Acanthamoeba and physiological mechanisms of the department is continually applying skin rash known as herpes zoster (Tanhehco and Colby, Cornea, corneal swelling and edema—major James Chodosh, MD, MPH or shingles. If the rash affects any September 2010) infections at pathological processes that con- Professor of Ophthalmology, Harvard Medical School laboratory discoveries to clinical practice. part of the eye, it is known as herpes Mass. Eye and Ear in recent years, tribute to corneal clouding. These Fellowship Director, Cornea Service, Massachusetts Eye With increasing success, we’re treating or zoster ophthalmicus (HZO). About paralleling nationwide trends. In discoveries form the basis of many and Ear Infirmary 10-20 percent of shingles patients addition, filamentous fungi were techniques currently used to restore averting the potentially devastating effects develop HZO, which can cause se- found to have replaced yeasts as the corneal clarity and visual acuity in Dr. James Chodosh, HMS Professor of Ophthalmol- of corneal disease, infections and injury. vere corneal damage (keratopathy) predominant pathogens in fungal patients. ogy and an investigator in the Howe Laboratory and blindness. With approximately keratitis at Mass. Eye and Ear. Soft Viral Pathogenesis Unit, is internationally known and 200,000 new cases each year in the contact lens wear was a major Investigating the respected for his work on molecular virology, viral United States—and the overall num- risk factor for developing either mechanisms of corneal genomics, and viral epidemiology. His laboratory conjunctiva. There are many causes ber of herpes zoster cases expected infection. By pinpointing the major clarity leads the field of ocular adenoviral pathogenesis of keratoconjunctivitis, including to increase—HZO poses a serious pathogens and risk factors involved For decades, it was unclear how the and epidemic keratoconjunctivitis (EKC), and has CORNEAL INFECTIONS allergens, microbes, and chemicals; public health concern. in atypical keratitis, this work may cornea maintains its avascular state. contributed greatly to the prevention and treat- The cornea protects the rest of the however, adenoviral keratoconjunc- Deborah Langston, MD, FACS, an lead to improved prevention and To retain clarity, it must prevent the ment of vision loss due to infection, corneal inflam- eye from injuries and microbial tivitis is particularly contagious, and expert in viral eye disease, recently treatment strategies for these development of blood vessels. In mation, and scarring. Dr. Chodosh is also committed pathogens, such as bacteria, fungi, spreads so rapidly that it commonly described a patient who developed potentially blinding infections. the July 25, 2006 issue of Proceedings to promoting the use of the Boston Keratoprosthe- or viruses; however, because it is causes epidemic keratoconjunctivi- corneal ulceration and secondary of the National Academy of Sciences sis (KPro) worldwide, and has performed and as- constantly exposed, the cornea itself tis (EKC). Although EKC infections bacterial and fungal infections due (PNAS), a team of researchers led sisted with artificial cornea implantation surgery in is susceptible to infections that may generally resolve on their own, the to HZO. Because a standard corneal by Reza Dana, MD, MSc, MPH India, Italy, England, and Israel. Recently, he began a cause keratitis, or corneal inflamma- inflammatory immune responses transplant would have likely failed in CORNEAL CLARITY revealed a novel role for vascular project to develop a $50 KPro for use in underprivi- tion. Besides causing irritation, pain, in the cornea may lead to corneal this case, the patient received a Bos- The focusing power of the cornea endothelial growth factor receptor leged nations. In collaboration with Claes Dohlman, and blurry vision, keratitis can dam- clouding that may linger for several ton Keratoprosthesis (KPro), devel- relies on its clarity. Many condi- 3 (VEGFR3) in maintaining corneal MD, PhD, Dr. Chodosh is studying how to improve age or scar the cornea, and may lead weeks, months, or even years in oped by Claes Dohlman, MD, PhD, tions—from injuries to infections to avascularity. Prior to this study, keratoprosthesis surgery outcomes by regulating to permanent vision loss. Several severe cases. to successfully replace the severely dietary or genetic deficiencies—can scientists believed that only lym- immune responses. scientists in the HMS Department of James Chodosh, MD, MPH and damaged cornea. Inflammation cause the cornea to lose transpar- phatic vessels and proliferating Dr. Chodosh is a committed teacher and mentor, Ophthalmology are conducting re- his team generated the first mouse subsided within a week of surgery, ency, and thus its ability to properly blood vessels expressed VEGFR3; and is Fellowship Director for Mass. Eye and Ear’s search and improving treatments for model of adenoviral keratitis, as well and vision gradually improved over refract light. Inflammatory respons- however, Dr. Dana and colleagues Cornea Service. He has authored over 110 articles this potentially blinding condition. as the first whole genome sequences
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