UW Department of Ophthalmology: FACULTY RESEARCH

CHEN, Philip P., MD
Current research interests include diagnosis, treatment methods (medical and surgical) and outcomes of treatment of open-angle and angle-closure glaucoma. Dr. Chen also performs anterior segment surgery.

CHUANG, Elaine L., MD
Elaine L. Chuang has advanced training and experience in medical and surgical diseases of the retina and vitreous diseases. Dr Chuang's current clinical interests focus primarily on ocular problems associated with two systemic conditions, Acquired Immunodeficiency Syndrome (AIDS) and sickle cell diseases. In the past, she has participated in clinical trials which have resulted in better understanding and treatments of age-related macular degeneration, retinal vein occlusion and diabetic eye disease, in addition to HIV infection and sickle eye disease.

HAESELEER, Françoise J., PhD
As in many signaling pathways, Ca2+ plays a critical role in visual perception. In neuronal cells, Ca2+-influx triggers the release of neurotransmitters at synapses. Additionally, in photoreceptor cells, Ca2+ plays a crucial role in modulating the recovery after activation of phototransduction. The activation of this cascade results in the hydrolysis of cGMP by cGMP phosphodiesterase and the closure of cGMP-gated ion channels. The ultimate consequence is a decrease of the cytoplasmic [Ca2+], because the Na+/Ca2+-K+ exchanger continues to remove Ca2+ from the cell while the influx of a Ca2+ through the channel is stopped. This is the change of [Ca2+], which is the key to light adaptation. Even though Ca2+ plays an important role in light adaptation, only the activation of guanylate cyclase by guanylate cyclase-activating protein in response to a decrease in cytoplasmic [Ca2+] has been well understood. Other key enzymes involved in the phototransduction cascade have been shown to be modulated in response to changes in [Ca2+], although the molecular identity of their modulator has yet to be determined.

Our objective is to molecularly identify and characterize novel neuronal Ca2+-binding proteins from retina using a panel of genetic and biochemical strategies. Our previous studies have identified novel Ca2+-binding proteins, named CaBPs. It is now essential to determine the function of these proteins in the retina. Two of these CaBPs, CaBP1 and CaBP5, are expressed in bipolar cells, a cell type that has not been as well characterized as photoreceptor cells. These new proteins offer the opportunity to analyze the molecular mechanism of action of modulators of bipolar cell functions. The study of retinal Ca2+-binding protein is important, not only to elucidate their role in retinal function and pathologies, but to potentially determine a similar characterization of homologous proteins in other biological systems.

KALINA, Robert E., MD
Robert E. Kalina has advanced training and experience in diseases of the retina. Special interests include Retinopathy of Prematurity, Intraocular Tumors (including Retinoblastoma and Melanoma), Retinal Degenerations (including Retinitis Pigmentosa and Macular Degeneration), and Eye Manifestations of Inherited Diseases.

KINYOUN, James L., MD
James L. Kinyoun has advanced training and experience in retina and vitreous diseases, particularly diabetic retinopathy. Clinical studies of drug and laser therapy for eye complications of diabetic eye disease have been his primary research interest. He has been an investigator in several collaborative clinical trials including the Diabetic Retinopathy Study, the Early Treatment Diabetic Retinopathy Study, the Diabetes Control and Complications Trial, and the Protein Kinase C ß Inhibitor Trial that is divided into two studies: the Diabetic Retinopathy Study and Diabetic Macular Edema Study.

MUDUMBAI, Raghu, MD
Raghu Mudumbai has advanced training and experience in neuro-ophthalmology, glaucoma, orbit, and oculoplastics.

ORCUTT, James C., MD, PhD
James C. Orcutt's research interests are in the areas of thyroid eye disease, orbital lymphomas, and a nonsurgical management of orbital disease. Cooperative surgical and clinical approaches with otolaryngology (head and neck surgery), neurosurgery, facial plastic surgery, surgical dermatology, and neuroradiology are of particular interest.

SAARI, John C., PhD
Light isomerizes 11-cis-retinal, the chromophore of vertebrate visual pigments; activates rhodopsin; and initiates the phototransduction cascade of reactions. The product of photoisomerization, all-trans-retinal, enters into a reaction pathway that regenerates the 11-cis-configuration and the native visual pigment. At any given physiologic level of illumination, a steady state is established in which the rate of visual pigment photoisomerization is equal to, and opposed by, the rate of regeneration. The log-sensitivity of the retina is inversely proportional to the steady-state level of bleached visual pigment. Thus, phototransduction, regeneration, and visual sensitivity are tightly linked in a process that has been called the visual pigment.

Work in my laboratory is directed towards obtaining a molecular understanding of visual cycle reactions and retinoid transport processes. Recent studies employing high performance liquid chromatography (HPLC) analysis of visual cycle intermediates demonstrated that all-trans-retinal is the only retinoid that accumulates during steady-state cycling of the mouse visual system and that the rate of regeneration is very similar to the rate of decay of all-trans-retinal. This implies that all reactions and processes of the visual cycle that follow reduction of all-trans-retinal are rapid and that all-trans-retinol dehydrogenase (RDH) catalyzes a slow step. Thus, reduction of all-trans-retinal by RDH plays a pivotal role in the visual cycle because its rate determines entry of all-trans-retinal into the regeneration pathway, and it is the ultimate quenching reaction of phototransduction.

Analysis of the retinoid composition and rhodopsin kinetics of transgenic mice is providing novel information about the roles of retinoid-binding proteins and phototransduction components in the visual cycle. Studies of the enzymology and molecular biology of visual cycle enzymes and proteins (for instance, all-trans-retinol dehydrogenase of photoreceptor cells and cellular retinaldehyde-binding protein of retinal pigment epithelium) will provide important tools for continued studies of the role of these components in inherited retinal diseases.

TOOP, James, OD, PhD
James Toop has broad experience in designing and fitting a wide variety of contact lenses. This includes lenses for all kinds of refractive errors, including large amounts of astigmatism. He has also fit many contacts post-surgically, as well as a number of soft cosmetic lenses to mask disfigured eyes.

WEISS, Avery H., MD
Avery H. Weiss has advanced training and experience in pediatric ophthalmology and strabismus, and refractive surgery. Specialties include the evaluation and treatment of infants and children with amblyopia, strabismus and abnormal eye movements, cataracts, glaucoma, infections, and lacrimal and eyelid abnormalities. Special areas of interest include comprehensive evaluation of infants and children with ocular problems related to birth defects, metabolic genetic, immunologic or neurologic diseases, and underlying prematurity or malignancies. Dr. Weiss has special expertise in the evaluation of the infant who doesn't see and the child who loses vision; treatment of retinoblastoma and orbital tumors; treatment of corneal cysteine accumulation in cystinosis; evaluation of children with congenital or acquired disorders of retinal function; evaluation and treatment of juvenile rheumatoid arthritis (JRA)-associated uveitis; cataract surgery with intraocular lens implantation in children; and treatment of adult strabismus.

Research interests include: Assessment of visual function and development, including the ability to quantitate vision in preverbal infants or nonverbal children using behavioral and visual-evoked potential (VEP) techniques -- Learning more about the development of normal eye movements and the underlying basis of abnormal eye movements and strabismus using eye movement recording techniques and other laboratory measures -- Characterization of the molecular basis of congenital cataracts by analyzing lens proteins -- Assessment of retinal function in infants and children with congenital and acquired retinal disorders using Electroretinograms (ERGs) and other diagnostic techniques.