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Ophthalmic Genetics and Visual Function Branch

Ophthalmic Genetics and Visual Function Branch
Building 10, Room 10N226
10 Center Drive, MSC 1860
Bethesda, Maryland 20892-1860
Phone: 301-496-3577
Fax: 301-402-1214

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Mission Statement

The Ophthalmic Genetics and Visual Function Branch plans and conducts clinical and laboratory research of gene expression, molecular genetics, cell biology, and molecular interactions important to the eye, and applies clinically relevant research findings to the prevention, diagnosis, and treatment of diseases affecting the eye and the visual system.


The Ophthalmic Genetics and Visual Function Branch comprises the following staff:

Name Title E-mail
Christian Antolik, Ph.D. Biologist antolikc@mail.nih.gov
Kapil Bharti, Ph.D.
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Stadtman Tenure-track Investigator kapilbharti@nei.nih.gov
Delphine Blain, Sc.M., M.B.A.
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Certified Genetic Counselor dblain@mail.nih.gov
Brian Brooks, M.D., Ph.D.
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Senior Investigator BrooksB@mail.nih.gov
Janine Davis, Ph.D. Staff Scientist Davisj@nei.nih.gov
Monika Dolinska Research Associate Dolinskam@nei.nih.gov
Benedetto Falsini, M.D.
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Adjunct Investigator falsinib@nei.nih.gov
Alexandra Garafalo, B.S. Research Assistant, eyeGENE® garafaloav@nei.nih.gov
Catherine Geer Administrative Laboratory Manager geerc@nei.nih.gov
Kerry Goetz, M.S. Health Science Program Manager, eyeGENE® Coordinator eyeGENEinfo@nei.nih.gov
Fielding Hejtmancik, M.D., Ph.D.
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Senior Investigator F3h@helix.nih.gov
Brett Jeffrey, Ph.D.
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Staff Scientist jeffreybg@nei.nih.gov
Xiaodong Jiao, M.D. Biologist jiaox@nei.nih.gov
Zhiwei Ma, M.D., Ph.D.
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Staff Scientist mazh@nei.nih.gov
Jairo Mejia Program Assistant mejiae@nei.nih.gov
Vida Ndifor, M.S. Senior Research Assistant, eyeGENE® ndiforv@nei.nih.gov
Rebecca Parrish Research Assistant, eyeGENE® parrishsr@nei.nih.gov
Melissa Reeves, M.S. Technical Laboratory Manager eyeGENEinfo@nei.nih.gov
Tumminia, Santa, Ph.D. Program Officer, eyeGENE® eyeGENEinfo@nei.nih.gov
Yuri Sergeev, Ph.D.
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Staff Scientist Yuri.V@nih.gov
Amy Turriff, Sc.M.
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Certified Genetic Counselor Turriffa@nei.nih.gov
Xinjing Wang, M.D., Ph.D.
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Staff Scientist Wangx6@nei.nih.gov
Wadih Zein, M.D.
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Staff Clinician zeinw@nei.nih.gov

(Click on the name of the Section to see its activities)

Section/Unit Contact E-mail Phone Number
Unit on Ocular and Stem Cell Translational Research Kapil Bharti, Ph.D. kapilbharti@nei.nih.gov 301-451-9372
Section on Pediatric, Developmental and Genetic Ophthalmology Brian Brooks, M.D., Ph.D. brooksb@nei.nih.gov 301-496-3577
Ophthalmic Molecular Genetics Section J. Fielding Hejtmancik, M.D., Ph.D. f3h@helix.nih.gov 301-496-8300
DNA Diagnostics Laboratory Xinjing Wang, M.D., Ph.D. Wangx6@nei.nih.gov 301-435-4568
Visual Function Brett Jeffrey, Ph.D. jeffreybg@nei.nih.gov 301-402-2391
eyeGENE® Santa Tumminia, Ph.D. eyeGENEinfo@nei.nih.gov 301-435-3032

Research Overview

As a center of excellence for clinical investigation, basic research and treatment of heritable ocular disorders, the Branch aims to understand developmental, genetic, molecular and cellular aspects of ocular biology in health and disease and to enable, broaden, and strengthen basic and translational science throughout NEI. An overarching goal is to identify the underlying genes, genetic networks, and drug targets in disease and to utilize this knowledge to increase understanding of vision biology and for the rational development of successful therapeutic interventions to slow or reverse disease progression.

The Ophthalmic Genetics Branch has a team of skilled and devoted clinician scientists, molecular geneticists, genetic counselors, and technologists, who have at their disposal a strong array of clinical and molecular genetic diagnostic tools for the investigation of families and patients with inherited retinal disorders. Over many years of clinical research, the Branch has compiled an impressive database of patients with fully characterized phenotypic information on a host of heritable ocular disorders. These disorders are amenable to further molecular genetic analysis and to future treatment protocols.

The Branch also provides:

  • Targeted clinical protocols for heritable ocular disorders.
  • A research infrastructure that supports the investigation and molecular genetic diagnosis of heritable ocular diseases. Part of that activity includes oversight of the National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE®) established by NEI.
  • Training opportunities in the basic and clinical sciences for the next generation of vision scientists in the investigation and treatment of inherited ocular disorders.

Some of the Branch’s research interests include:

  • ABCA4 Retinopathy

    ABCA4 is a photoreceptor protein important in the recycling of retinoids during the visual cycle. Mutations in the ABCA4 gene lead to a spectrum of phenotypes. The most common presentation is Stargardt disease, where central vision loss develops in the first few decades of life, often accompanied by retinal flecks composed of lipofuscin and macular atrophy. More severely affected patients may develop a more widespread cone-rod or rod-cone degeneration.

    Recently, several approaches to slowing or stopping the progression of ABCA4 retinopathy have been proposed, including gene therapy, stem cell based therapy and small molecule therapy. Therapeutic trials are on the horizon. However, because most patients with ABCA4 retinopathy progress at a slow rate, determining whether a treatment strategy is effective will depend upon developing robust clinical outcome measures that can be observed over a relatively short period of time.

    To this end, we have established a natural history protocol for patients with ABCA4 retinopathy. The goals of this clinical research protocol are to determine which clinical tests are likely to be the most useful outcome variables in a future clinical trial and to better understand the genetic factors that regulate the severity of disease/rate of progression.

  • Achromatopsia
  • Albinism

    Albinism is an inherited disorder characterized by reduced melanin pigment in the hair, skin and eyes. For reasons that are not completely clear, patients with albinism also have several developmental eye abnormalities that limit their best-corrected visual acuity, including foveal hypoplasia and an abnormal projection pattern of their optic nerve pathways. This observation raises an important clinical question-if we had a way of improving pigmentation at early stages of postnatal development, when the fovea is still maturing, could we improve vision in patients with albinism.

    We have recently shown that nitisinone, an FDA-approved drug used in the treatment of hereditary tyrosinemia, type1 (HT1), is able to improve ocular and fur pigmentation in a mouse model of one form of albinism, OCA1B. We are currently researching whether this compound may be effective in other mouse models of albinism. We are also developing a pilot clinical trial to determine whether nitisinone is effective in improving melanin pigment in adult patients with OCA1B. If it is effective, we intend to extend this trial to include more patients, including those of younger ages. Another goal of this trial is to determine which clinical outcome measures are most useful in treating patients with albinism.

    In parallel, we are attempting to develop other treatment strategies for albinism that may work via different mechanisms, mostly focused on tyrosinase-the first and rate-limiting step in melanin production. These studies remain at the pre-clinical stage and include ways of improving intrinsic tyrosinase activity, improving the intracellular trafficking/folding of tyrosinase, and increasing the expression level of tyrosinase.

  • Coloboma

    Uveal coloboma is a potentially-blinding congenital ocular malformation caused by the failure of the optic fissure to close during the 5th week of human gestation. Uveal coloboma is most often sporadic, although autosomal dominant, autosomal recessive and X-linked pedigrees have been described. Our current understanding of the genetics of uveal coloboma is limiting, making genetic counseling and molecular diagnosis difficult.

    A major goal of our research is to understand the developmental mechanisms and the genetics of uveal coloboma in order to better serve patients and their families. We also seek to understand other systemic medical issues patients with coloboma experience.

  • Dark Adaptation in Age-Related Macular Degeneration
  • eyeGENE®
    The eyeGENE® Network is a national genetics initiative, which enables research into the causes and mechanisms of inherited eye diseases. The fundamental purpose of the eyeGENE® Network is to foster and support research into the genetic causes of ophthalmic disorders. This is accomplished by broadening patient and family access to genetic diagnostic testing and by creating and maintaining a national repository of genetic samples from highly characterized individuals and families to allow investigations of the causes, interventions, managements, and cures of genetic eye disorders. The Network, a component of the NEI Intramural Research Program, is a model partnership between the government, eye health care providers, CLIA-approved molecular diagnostic laboratories, private industry, and extramural scientists who support a broad research constituency.

    In brief outline the Network incorporates three essential elements:

    • Community-based health care providers submit a patient’s blood sample and receive a DNA molecular evaluation for diagnosis and genetic counseling.
    • Patients contribute their sample and information to a protected, de-identified registry. They may elect to be notified of their eligibility to participate in clinical trials testing investigational therapies.
    • Researchers have access to de-identified DNA samples and clinical information to investigate genotype/phenotype relationships and the causes of eye disease.

    The eyeGENE® Network currently includes CLIA diagnostic laboratory partners, >250 registered clinical organizations (with >400) registered users from around the nation (and Canada), and is now testing 70 genes for over 30 inherited eye diseases.

  • Genetic Determinants of Plaquenil Toxicity
  • Induced Pluripotent Stem Cells (iPSCs) to Study and Treat Retinal Pigment Epithelium Disorders
    Dysfunctions in the retinal pigment epithelium (RPE) of the eye are thought to be the initiating events leading to degenerative eye diseases. Therefore, a better understanding of the disease initiating pathways in RPE will provide a basis for therapeutic interventions. In vitro disease models are being developed to study patient-specific disease processes, to set up high through drug screens, and to develop cell-based therapy for retinal degenerative diseases. Skin biopsies from patients with clinically diagnosed degenerative eye diseases are being used to derive iPS cells. RPE cells differentiated from such iPS cells are used to study events that have led to disease initiation and progression. In collaboration with the NIH Center for Advancing Translational Sciences, we are developing high throughput screens to identify small molecules that can provide potential therapeutic interventions for such degenerative eye diseases. In collaboration with the new NIH Center for Regenerative Medicine, we are developing clinical-grade iPSC-derived RPE tissue for cell-based therapy, in compliance with current Good Manufacturing Practices.
  • Inherited retinal degenerations and allied diseases
  • Molecular Genetics of Inherited Eye Disease

    This section has been involved in a number of different to study inherited visual diseases affecting the lens and retina as well as diseases affecting multiple ophthalmic structures such as glaucoma and myopia.

    One approach to understanding inherited visual diseases uses principles of positional cloning to identify genes important in human inherited diseases. Such diseases currently undergoing linkage analysis, gene isolation, or characterization of mutations include Usher syndrome, retinal degenerations, inherited cataracts, Bietti crystalline dystrophy, corneal dystrophies, glaucoma, and high myopia.

    A second approach is to attempt to establish associations between sequence changes in candidate genes and specific phenotypes. This type of study is most applicable to prevalent multifactorial diseases with a complex inheritance pattern, and is currently being used for age related cataracts, myopia, and glaucoma.

    Once a candidate gene has been identified and confirmed, the biochemical and pathophysiological implications of identified mutations are explored both in vitro through recombinant expression of native and mutant proteins and in vivo through transgenic expression of pathological proteins in a variety of model systems including transgenic and knockout mice and zebrafish, These approaches provide both increased understanding of vision biology and the basis for rational design of diagnostic and therapeutic approaches.

  • Usher Syndrome
  • X-linked Juvenile Retinoschisis
Last Reviewed: 
December 2014