Article

Non-Invasive Stem Cell Therapy in a Rat Model for Retinal Degeneration and Vascular Pathology

Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
PLoS ONE (Impact Factor: 3.53). 02/2010; 5(2):e9200. DOI: 10.1371/journal.pone.0009200
Source: PubMed

ABSTRACT Retinitis pigmentosa (RP) is characterized by progressive night blindness, visual field loss, altered vascular permeability and loss of central vision. Currently there is no effective treatment available except gene replacement therapy has shown promise in a few patients with specific gene defects. There is an urgent need to develop therapies that offer generic neuro-and vascular-protective effects with non-invasive intervention. Here we explored the potential of systemic administration of pluripotent bone marrow-derived mesenchymal stem cells (MSCs) to rescue vision and associated vascular pathology in the Royal College Surgeons (RCS) rat, a well-established animal model for RP.
Animals received syngeneic MSCs (1x10(6) cells) by tail vein at an age before major photoreceptor loss. Principal results: both rod and cone photoreceptors were preserved (5-6 cells thick) at the time when control animal has a single layer of photoreceptors remained; Visual function was significantly preserved compared with controls as determined by visual acuity and luminance threshold recording from the superior colliculus; The number of pathological vascular complexes (abnormal vessels associated with migrating pigment epithelium cells) and area of vascular leakage that would ordinarily develop were dramatically reduced; Semi-quantitative RT-PCR analysis indicated there was upregulation of growth factors and immunohistochemistry revealed that there was an increase in neurotrophic factors within eyes of animals that received MSCs.
These results underscore the potential application of MSCs in treating retinal degeneration. The advantages of this non-invasive cell-based therapy are: cells are easily isolated and can be expanded in large quantity for autologous graft; hypoimmunogenic nature as allogeneic donors; less controversial in nature than other stem cells; can be readministered with minor discomfort. Therefore, MSCs may prove to be the ideal cell source for auto-cell therapy for retinal degeneration and other ocular vascular diseases.

Download full-text

Full-text

Available from: Grazyna Adamus, Aug 17, 2015
0 Followers
 · 
202 Views
  • Source
    • "In particular, secretion of neuroprotective and immuno-modulatory molecules suggest significant therapeutic potential [1]. Most pertinent to the present study, previous reports have already demonstrated a retinal neuroprotective effect with MSCs delivered either by intravenous or intravitreal injection [16], [17]. In addition, ex vivo genetic modification of MSCs could extend the range of therapeutic benefits of MSC therapy [18]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mesenchymal stem cells (MSCs) have well-established paracrine effects that are proving to be therapeutically useful. This potential is based on the ability of MSCs to secrete a range of neuroprotective and anti-inflammatory molecules. Previous work in our laboratory has demonstrated that intravenous injection of MSCs, treated with superparamagnetic iron oxide nanoparticle fluidMAG-D resulted in enhanced levels of glial-derived neurotrophic factor, ciliary neurotrophic factor, hepatocyte growth factor and interleukin-10 in the dystrophic rat retina. In this present study we investigated whether the concentration of fluidMAG-D in cell culture media affects the secretion of these four molecules in vitro. In addition, we assessed the effect of fluidMAG-D concentration on retinoschisin secretion from genetically modified MSCs. ELISA-assayed secretion of these molecules was measured using escalating concentrations of fluidMAG-D which resulted in MSC iron loads of 0, 7, 120, or 274 pg iron oxide per cell respectively. Our results demonstrated glial-derived neurotrophic factor and hepatocyte growth factor secretion was significantly decreased but only at the 96 hour's time-point whereas no statistically significant effect was seen with ciliary neurotrophic factor secretion. Whereas no effect was observed on culture media concentrations of retinoschisin with increasing iron oxide load, a statistically significant increase in cell lysate retinoschisin concentration $({rm p}=0.01)$ was observed suggesting that increasing fluidMAG-D concentration did increase retinoschisin production but this did not lead to greater secretion. We hypothesize that higher concentrations of iron-oxide nanoparticle fluidMAG-D have an effect on the innate ability of MSCs to secrete therapeutically useful molecules and also on secretion from genetically modified cells. Further work is required to verify these in vitro finding using - in vivo model systems.
    IEEE Transactions on Magnetics 01/2013; 49(1):389-393. DOI:10.1109/TMAG.2012.2225829 · 1.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The retina and associated supportive tissues must perform large amounts of metabolic work to effectively process visual information. Metabolic imbalances in these tissues can lead to various diseases of the back of the eye that generally involve the interplay of three major processes: inflammation, neovascularization, and degeneration. Improved understanding of these processes within the back of the eye has led to the development of a rather large number of new therapeutics over the last decade and this process shows no sign of slowing down. This chapter summarizes emerging drug targets, new drugs, and drugs undergoing clinical trials for treating various back of the eye diseases including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, infections, and autoimmune uveitis.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Monogenic human retinal dystrophies are a group of disorders characterized by progressive loss of photoreceptor cells leading to visual handicap. Retinitis pigmentosa is a type of retinal dystrophy where degeneration of rod photoreceptors occurs at the early stages. At present, there are no available effective therapies to maintain or improve vision in patients affected with retinitis pigmentosa, but post-genomic studies are allowing the development of potential therapeutic approaches. This review summarizes current knowledge on genes that have been identified to be responsible for retinitis pigmentosa, the involvement of these genes in the different forms of the disorder, the role of the proteins encoded by these genes in retinal function, the utility of genotyping, and current efforts to develop novel therapies.
    Genome Medicine 05/2010; 2(5):34. DOI:10.1186/gm155 · 4.94 Impact Factor
Show more