ophth_logo


Laboratory of Dr. Robert F. Mullins
The University of Iowa
Department of Ophthalmology and Visual Sciences

 

shapeimage_2The major focus of our laboratory is to understand the cellular and molecular basis of human retinal diseases, including age-related macular degeneration (AMD), central serous retinopathy and Best vitelliform macular degeneration.

 

We are especially interested in the role of the choroid in the development of AMD and other macular diseases. The choroid is a layer of the eye containing a rich vascular supply that provides nutrients to the photosensitive rods and cones of the retina. In addition to its role in nourishing the retina, the choroid plays important roles in retinal pathology in AMD. The endothelial cells that form the blood vessels of the choroid can become activated to migrate, divide and invade the retina, in the neovascular or “wet” form of AMD. We are exploring the mechanisms of how these cells become abnormally activated, to determine how we can arrest this process.

 

In addition to causing “wet” AMD, our laboratory has found that loss of capillary endothelial cells occurs very early in the dry form of AMD as well. Thus, both excessive and insufficient activity of the blood vessels in the choroid contribute to macular degeneration. With new developments in stem cell technology, we are exploring the replacement of dead cells with stem cell derived endothelial cells.

 

In addition to AMD, we are interested in the pathogenesis of other macular diseases, particularly Best disease, a genetic form of macular degeneration with an early onset. Our laboratory is interested in understanding how mutations in the gene BEST1 lead to the distinct macular “egg yolk” lesion, why the lesions tend to form in the macula and spare the extramacular retina, and what other genetic factors interact with the BEST1 gene product to modify the Best disease phenotype.

 

We utilize animal models, human donor eyes, cell culture approaches, biochemical methods and genetic resources unique to the Carver Family Center for Macular Degeneration to approach these problems.

 

We also actively work with colleagues at the CFCMD and University of Iowa Institute for Vision Research and around the world in the study of other retinal diseases including Bardet-Biedl syndrome, Stargardt disease, Leber congenital amaurosis, retinitis pigmentosa, uveitis, and other acquired and inherited diseases of the retina.

 

It is our hope that these studies into the molecular and cellular basis of choroidal and retinal degenerations will lead to improved treatments for the millions of individuals whose sight is threatened by retinal diseases.

Mullins Lab Photos

  • ITGB1 Cd29 Choroid

  • Dividing Endothelial Cells

  • Druse

  • Drusen Complement

  • Cone Photoreceptors

  • Endothelial Cell Migration

  • Choroid Retina ICAM2

  • Endothelial Cell Actin

ITGB1 Cd29 Choroid

ITGB1 Cd29 Choroid

Immunofluorescence image of beta-1 integrin/CD29 labeling in blood vessels of the choriocapillaris (CC).  The yellow autofluorescence of the retinal pigment epithelium (RPE) is due to the accumulation of lipofuscin, which occurs in aging eyes.

Dividing Endothelial Cells

Dividing Endothelial Cells

Scanning electron micrograph of dividing endothelial cells.

Druse

Druse

Histology of a druse (plural, drusen) from a human donor eye. Drusen are presymptomatic risk factors for AMD that develop between the retinal pigment epithelium(RPE) and its blood supply, the choroiocapillaris (CC).

Drusen Complement

Drusen Complement

Drusen from a human donor eye with AMD, labeled with an antibody directed against terminal complement complex C5b-9 (green fluorescence) illustrates the role of immune-mediated processes in AMD. For details see Mullins et al., 2000, FASEB J, 14(7):835-46; Skeie et al., 2010, IOVS in press.

Cone Photoreceptors

Cone Photoreceptors

Immunohistochemical labeling of cone photoreceptor cells from a human retina. Nuclei are stained blue with a DNA-binding probe.

Endothelial Cell Migration

Endothelial Cell Migration

Scanning electron micrograph of a migrating choroidal endothelial cell. These cells become activated by elastin, which may be an important factor in macular degeneration. For details see Skeie and Mullins, Invest Ophthalmol Vis Sci 2008  49: 5574-80.

Choroid Retina ICAM2

Choroid Retina ICAM2

Localization of the endothelial cell adhesion molecule ICAM-2 (purple) in blood vessels of the retina and choroid.

Endothelial Cell Actin

Endothelial Cell Actin

Actin (green) staining of endothelial cells. Nuclei are labeled blue.