In this study, state of the art sequencing technologies were used to identify disease-causing mutations in the USH2A gene in an adult patient with autosomal recessive Retinitis Pigmentosa. Induced pluripotent stem cells (iPSCs), generated from the patient's skin, were differentiated into multi-layer eyecup-like structures with features of human retinal cells. The inner layer of the eyecups contained immature photoreceptor cells that expressed photoreceptor markers and exhibited cilia and basal bodies characteristic of outer segments.
Patient-specific iPSC-derived photoreceptor precursor cells as a means to investigate retinitis pigmentosaAugust 5th, 2013
August 5th, 2013
In 2010 scientists at the University of Iowa Wynn Institute for Vision Research discovered an RP-causing gene known as MAK. They have now embarked upon an ambitious project to cure this disease, which has three major goals.
1) Identify all patients in the United States who have retinitis pigmentosa caused by mutations in the MAK gene.
2) Develop gene-replacement therapy for younger individuals with this disease who still have a substantial amount of functioning retina remaining.
August 4th, 2013
Mutations in ABCA4 cause Stargardt disease and other blinding autosomal recessive retinal disorders. However, sequencing of the complete coding sequence in patients with clinical features of Stargardt disease sometimes fails to detect one or both mutations. For example, among 208 individuals with clear clinical evidence of ABCA4 disease ascertained at a single institution, 28 had only one disease-causing allele identified in the exons and splice junctions of the primary retinal transcript of the gene.
July 30th, 2013
Humans and mice with specific mutations in the BBS1 gene show progressive death of photoreceptor cells. In research recently published in Investigative Ophthalmology and Visual Sciences, Wynn Institute scientists made a virus containing a normal version of the mouse Bbs1 gene and injected the virus under the retina of mutant mice. When compared to untreated mice and untreated eyes in the same mice, the treated mice showed modest improvement in electrical responses in the retina and also showed partial restoration of normal retinal biochemistry.
July 29th, 2013
The purpose of this study was to determine whether a xeno-free synthetic cell culture surface (Synthemax™) could be used to aid in the production and subsequent retinal specific differentiation of clinical grade induced pluripotent stem cells (iPSCs). iPSCs were generated using adult somatic cells via infection with either a single excisable lentiviral vector or 4 separate non-integrating Sendai viruses driving expression of the transcription factors OCT4, SOX2, KLF4, and c-MYC.
Abnormal development of NG2+PDGFRα+ neural progenitor cells causes neonatal hydrocephalus in a ciliopathy mouse modelNovember 18th, 2012
Hydrocephalus is a common neurological disorder leading to expansion of the cerebral ventricles. Most neonatal cases are of unknown etiology and are likely to display complex inheritance involving multiple genes and environmental factors. We employed a hydrocephalic mouse model of the human ciliopathy Bardet-Biedl Syndrome (BBS) and identified a role for neural progenitors in the pathogenesis of neonatal hydrocephalus.
March 6th, 2012
The Research Eye Bank at the IVR enables scientists to study common and rare diseases. Scientists at the IVR recently had the first opportunity to characterize eyes from a donor with retinal degeneration due to mutations in the ABCA4 gene. This work, which combined human genetics with histology and state of the art microarray analysis, found that death of photoreceptor cells (rods and cones) occurs in advance of death of the retinal pigment epithelium (RPE).
Vitamins commonly prescribed for age-related macular degeneration reduce inflammation in blood vessel cellsJanuary 12th, 2012
The Age-Related Eye Disease Study (AREDS) combination of vitamins and zinc is commonly recommended to patients with age-related macular degeneration (AMD), but the mechanism whereby this regimen affects the progression of AMD has not been well studied. Wynn Institute scientists examined the effects of an AREDS vitamin solution on cells involved in AMD and found that treatment with vitamin solution reduces the adhesion between white blood cells and the endothelial cells that line blood vessels (see photo below), suggesting that inflammation in eyes with AMD may be reduced by the treatment.
December 24th, 2011
An essential step in the development of therapy for an inherited disease is to carefully characterize a cohort of affected patients to define the anatomical and temporal features of the disease. Such a study can identify the tissues that are the most relevant target for therapy as well as the points in the disease course where various treatments would have the greatest opportunity for benefit with the lowest risk.
November 3rd, 2011
The mechanisms controlling BBSome trafficking and the cargo proteins transported by the BBSome are not well understood. We hypothesized that by utilizing tandem affinity purification (TAP) we could identify novel regulators and cargos of the BBSome. Therefore, we generated transgenic mice expressing BBSome subunits with a TAP tag and performed tandem affinity purification using tissue from these mice to identify a novel protein, leucine-zipper transcription factor-like 1 (LZTFL1), as a BBSome interacting protein.