Retinal degeneration and related diseases are the leading cause of blindness and represent a major public health burden with economical and social impacts. As photoreceptor loss, the development of secondary vascular pathology causes disastrous consequences for vision. There is no effective treatment available. Our recent study revealed that a single intravenous injection of bone marrow derived mesenchymal stem cells (MSCs) at early stages of degeneration can preserve photoreceptors from death, sustain visual function, and limit pathological vascular changes in a rodent model of retinal degeneration. We propose to develop a treatment protocol that preserves vision and limits vascular pathology using non-invasive stem cell therapy in rodent models for retinal degeneration. We hypothesize that systemic administration of MSCs to treat ongoing retinal degeneration will slow the progress of photoreceptor loss and stabilize/repair the secondary vascular pathology by promoting the release of paracrine and autocrine mediators. The following specific aims are proposed: (1) Determine dose-response and long-term safety and efficacy of MSC treatment at early stages of degeneration in the RCS rat;(2) Investigate the neuro-vascular protective effects of MSCs at later stages of degeneration in the RCS rat and in Elovl4 mouse;(3) Examine the molecular mechanism of MSC homing to the retina and efficacy after intravenous administration. Based on the current extensive clinical experience using MSCs as therapy for both regenerative and degenerative medicine, if positive results are obtained in animal models, this treatment has a realistic likelihood of translation to the clinic.

Public Health Relevance

Retinal degeneration and associated ocular vascular pathology are the leading course of irreversible blindness in the USA, there is no effective treatment yet. We propose to develop non-invasive cell-based therapy to preserve vision and limit the pathological vascular modification by systemic administration of multipotent bone marrow derived stem cells (MSCs) in rodent models for retinal degeneration. The MSCs have great potential for clinic as autologous cells to rescue vision and stabilize/repair ocular vascular pathology.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Biology and Diseases of the Posterior Eye (BDPE)
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Neuhold, Lisa
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Cedars-Sinai Medical Center
Los Angeles
United States
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Jones, Melissa K; Lu, Bin; Girman, Sergey et al. (2017) Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases. Prog Retin Eye Res 58:1-27
Bakondi, Benjamin; Girman, Sergey; Lu, Bin et al. (2016) Multimodal Delivery of Isogenic Mesenchymal Stem Cells Yields Synergistic Protection From Retinal Degeneration and Vision Loss. Stem Cells Transl Med :
Jones, Melissa K; Lu, Bin; Saghizadeh, Mehrnoosh et al. (2016) Gene expression changes in the retina following subretinal injection of human neural progenitor cells into a rodent model for retinal degeneration. Mol Vis 22:472-90
Bakondi, Benjamin (2016) In vivo versus ex vivo CRISPR therapies for retinal dystrophy. Expert Rev Ophthalmol 11:397-400
Bakondi, Benjamin; Lv, Wenjian; Lu, Bin et al. (2016) In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa. Mol Ther 24:556-63
Tsai, Yuchun; Lu, Bin; Bakondi, Benjamin et al. (2015) Human iPSC-Derived Neural Progenitors Preserve Vision in an AMD-Like Model. Stem Cells 33:2537-49
Lu, Bin; Lin, Yanhua; Tsai, Yuchun et al. (2015) A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy. Transl Vis Sci Technol 4:7
Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V et al. (2014) Ocular changes in TgF344-AD rat model of Alzheimer's disease. Invest Ophthalmol Vis Sci 55:523-34
Lu, Bin; Morgans, Catherine W; Girman, Sergey et al. (2013) Neural Stem Cells Derived by Small Molecules Preserve Vision. Transl Vis Sci Technol 2:1
Swoboda, Jonathan G; Elliott, Jimmy; Deshmukh, Vishal et al. (2013) Small molecule mediated proliferation of primary retinal pigment epithelial cells. ACS Chem Biol 8:1407-11