The Fuhrmann Laboratory

Dr. Sabine Fuhrmann

Associate Professor of Ophthalmology and Visual Sciences
Adjunct Associate Professor of Neurobiology & Anatomy

University of Utah Health Sciences Center
John A. Moran Eye Center, Rm S3180
65 Mario Capecchi Drive
Salt Lake City, UT 84132

Email: sabine.fuhrmann@hsc.utah.edu
Phone: 801-581-4684
Fax: 801-587-8314

RESEARCH

Regulation of ocular development

The goal of our research is to understand the cellular and molecular mechanisms that regulate the patterning and differentiation of the vertebrate eye. Questions addressed in our lab include the following: How is eye development initiated in the anterior neuroepithelium, and what factors determine the early steps of eye formation? How is differentiation of ocular tissues controlled? What are the signals involved in these processes, and what are their downstream targets? Is there crosstalk between different pathways? How is homeostasis of ocular tissues maintained?

The vertebrate eye is formed through coordinated interactions between neuroepithelium, surface ectoderm, and extraocular mesenchyme. Following eye field formation, the neuroepithelium of the ventral forebrain evaginates, resulting in the formation of bilateral optic vesicles. Factors from surrounding tissues, extracellular factors, and intrinsic signals such as transcription factors control differentiation of the neural retina and retinal pigment epithelium (RPE) starting at the early optic vesicle stage.

One major focus in the lab is to investigate how the RPE develops. In the adult, the RPE is located between the retina and choroid in the posterior eye and consists of a monolayer of cuboidal, pigmented cells. It is vital for growth of the eye; improper develop¬ment results in congenital ocular defects such as microphthalmia, anophthalmia, or a change of cell fate resulting in loss of the RPE. Moreover, the RPE is absolutely critical for photoreceptor function and homeostasis in the adult eye. Thus, a better understanding of the mechanisms underlying RPE development and homeostasis may provide a basis for therapeutic treatments of ocular diseases such as macular degeneration and will be important for ocular stem cell biology. However, very little is known about the mechanisms that specify and maintain the RPE fate. We use conditional inactivation in mice in combination with tissue culture and biochemical and cell biological approaches to test the function of TGFbeta/Activin and Wnt signaling in RPE induction and differentiation as well as in RPE homeostasis in the adult eye.

RPE
Figure Legend:
Conditional disruption of ß-catenin in the embryonic mouse RPE leads to a loss of pigmentation (B; arrow) and abnormal thickening of the dorsal RPE (D; arrowhead), an initial sign of defective RPE formation. A,C: control eyes.
 

Patient Care Significance

Photo of multispectral image of mouse eye and retina.

Multispectral image of mouse
eye and retina.

Many inherited and some induced eye defects arise in utero and lead to devastating blindnesses. At present there is neither any cure for such defects, nor are they easy to detect in advance. Dr. Fuhrmann’s research is critical to the process of identifying genes associated with such events and is the first step in defining points of potential intervention. The Fuhrmann Laboratory is the Moran Eye Center’s lead team in identifying early eye gene defects and decoding their molecular interactions.

Selected Publications

1. Kruse-Bend R, Rosenthal J, Quist TS, Veien ES, Fuhrmann S, Dorsky RI, Chien CB (2012). Extraocular ectoderm triggers dorsal retinal fate during optic vesicle evagination in zebrafish. Dev Biol. 2012 Nov 1;371(1):57-65.

2. Fuhrmann S (2010) Eye morphogenesis and patterning of the optic vesicle. Current Topics in Developmental Biology. 93: 61-84. Invertebrate and Vertebrate Eye Development. Cagan RL and Reh TA (eds.), Elsevier, Academic Press.

3. Westenskow PD, McKean JB, Kubo K, Nagakawa S, Fuhrmann S (2010) Ectopic Mitf in the embryonic chick retina by co-transfection of b-catenin and Otx2. Invest Ophthalmol Vis Sci Oct. 51(10): 5328-5335

4. Bassett EA, Williams T, Zacharias AL, Gage PJ, Fuhrmann S, West-Mays JA (2010) AP-2a knockout mice exhibit optic cup patterning defects and failure of optic stalk morphogenesis. Hum Mol Genetics May 1;19(9):1791-1804

5. Westenskow P, Piccolo S, Fuhrmann S (2009) Beta-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development Aug;136(15)2505-10

6. Fuhrmann S, Riesenberg A, Mathiesen AM, Brown EC, Vetter ML, Brown NL (2009) Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. Invest Ophthalmol Vis Sci Jan;50(1):432-440