Unique Resources

Human Eye Donor Tissue Collection

In 2004, in collaboration with the Iowa Lions Eye Bank, we began to acquire human eye donor tissues to support the research activities of the entire Institute for Vision Research at the University of Iowa. The purpose of this collection is to discover the molecular basis of eye diseases and to provide the largest possible number of vision scientists in the group with the highest quality tissue. Faculty and staff members in various vision science laboratories share the responsibilities of collecting donor eyes on an “on call” basis, the majority of which are obtained after hours. Tissue specimens from the anterior and posterior segments are archived as frozen punches suitable for mRNA or protein isolation, as well as paraformaldehyde fixed tissue suitable for histological analysis.

Hematoxylin/Eosin stained sections are prepared from each sample in the collection. In addition, whole blood and/or extraocular muscle is collected from every donor so that DNA is available for genotype-phenotype correlation. To date, over 1,500 eyes have been archived in this manner. This collection contains samples from normal eyes, eyes with common diseases (including age-related macular degeneration, diabetic retinopathy, and glaucoma) and eyes with very rare diseases (retinoschisis, Best disease, and retinitis pigmentosa). A subset of the samples have extensive medical records including fundus photographs, fluorescein angiograms, intraocular pressure history, medications and other important clinical information. Studying this collection of eyes has given us new insights into common diseases like glaucoma and AMD, as well as rare inherited diseases like Best disease and retinitis pigmentosa.

We have shared these precious samples to advance disease research with scientists in Canada, the United Kingdom, and in the United States (e.g., California, Florida, Illinois, Kentucky, and Massachusetts). These tissues are used by members of our team for the purpose of expression studies, genotype phenotype correlation studies, immunohistochemistry experiments, and other studies relevant to the mission of the Institute in finding the cause, course and cure for blinding eye diseases.

Human Stem Cell Collection

With the advent of the induced pluripotent stem cell (iPSC), isolation of skin-derived fibroblasts and keratinocytes from patients with retinal degenerative disorders has greatly enhanced our ability to both find and interrogate new disease causing mutations and develop patient-specific transplantation approaches for disease treatment. We currently have a collection of greater than 1,300 patient biopsies and subsequent primary cell lines. Using this collection we recently generated iPSCs from retinitis pigmentosa (RP) patients with unknown causes of disease. These iPSCs were subsequently used to elucidate the pathogenic role of a newly identified RP causing mutation in the gene MAK (Tucker et. al., PNAS ) and has been used to determine the pathogenic mechanisms of mutations in other genes.

Prior to our ability to generate patient-specific stem cells, we were unable to directly study the role of specific disease-causing mutations within the human retina. Our ability to continue to expand our skin cell collection is critical to finding new disease-causing genes and developing new patient-specific treatments for people with RP and other blinding retinal degenerative disorders.

Our ability to continue to expand our skin cell collection is critical to finding new disease causing genes and developing new patient specific treatments for people with RP, choroideremia, age-related macular degeneration, and other blinding retinal degenerative disorders.

Human DNA Collection

In 1987, Dr. Stone began to collect DNA samples from patients affected with inherited eye diseases and this sample collection has steadily grown to the point that it is now the largest collection of its kind in the world. The collection now contains samples from more than 60,000 individuals with an inherited eye disease and 5,000 control individuals. The diagnoses represented in this collection range from very common disorders like macular degeneration and glaucoma to much more rare conditions like Bardet Biedl Sydrome, Stargardt disease and Leber Congenital Amaurosis (LCA). At the time of this writing, the collection contains samples from over 900 individuals with LCA, which represents one fourth of the entire LCA patient population in the United States. The DNA sample repository has robotic DNA extraction instrumentation and a barcode-based laboratory information management system that is capable of processing 20,000 samples per year.

In addition, every sample added to the repository is screened with forensic DNA markers to ensure the authenticity (sex and family relationships) of the samples. Approximately one fourth of the samples in the collection were contributed by individuals seen as patients in the Ophthalmology Department of the University of Iowa while the remainder were contributed by clinician scientists at other institutions across the United States and from more than 20 other countries. All of the members of the Institute for Vision Research have access to the samples in this repository on a collaborative basis for the purpose of new disease gene discovery, genotype/phenotype correlation, and identification of disease modifying genes. In addition, all members of the group have free access to the instrumentation and personnel necessary for additional sample acquisition.

The Stephen W. Dezii Translational Vision Research Facility

The Stephen W. Dezii Translational Vision Research Facility located within the Institute for Vision Research is a state-of-the-art ISO Class 5/6 biomedical human research current good manufacturing practice (cGMP) laboratory. This cGMP facility will be used for the culture of xeno-free patient-specific iPSC cell lines for future human transplantation trials, as well as the clean and expedited production of our own in-house adeno-associated viral particles for use in human gene augmentation and gene replacement trials.

Computational Resources

Access to super-computing clusters including Neon (3800 cores, gt. 26 TB of RAM) and Helium (3508 cores, 11 TB of RA M) as well as 80 TB of fast storage dedicated to eye research; and locally-customized pipelines and procedures for processing massively parallel sequencing data from DNA (custom capture, exome and genome) and RNA (mRNA, miRNA, RNA editing) experiments.

Clinical