BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function

Autor: Biju B. Thomas, Robert B. Aramant, Magdalene J. Seiler, Melissa J. Mahoney, Zhenhai Chen, Srinivas R. Sadda, S. Arai, Sridhar Chadalavada
Rok vydání: 2008
Předmět:
Retinal degeneration
Motion Perception
Medical Biochemistry and Metabolomics
Ophthalmology & Optometry
Animals
Genetically Modified
chemistry.chemical_compound
Neurotrophic factors
Evoked Potentials
Stem Cells
Retinal Degeneration
Microspheres
Sensory Systems
Mutant Strains
Electrophysiology
Treatment Outcome
medicine.anatomical_structure
Head Movements
Immunohistochemistry
Visual
Superior Colliculi
medicine.medical_specialty
Genetically Modified
Biology
Rats
Mutant Strains
Article
Retina
Cellular and Molecular Neuroscience
Opthalmology and Optometry
Internal medicine
medicine
Animals
Brain-derived neurotrophic factor
Animal
Brain-Derived Neurotrophic Factor
Superior colliculus
Neurosciences
Retinal
medicine.disease
Rats
Transplantation
Disease Models
Animal
Ophthalmology
Endocrinology
nervous system
chemistry
Disease Models
Evoked Potentials
Visual
sense organs
Neuroscience
Photic Stimulation
Stem Cell Transplantation
Zdroj: Experimental eye research, vol 86, iss 1
Seiler, MJ; Thomas, BB; Chen, Z; Arai, S; Chadalavada, S; Mahoney, MJ; et al.(2008). BDNF-treated retinal progenitor sheets transplanted to degenerate rats: Improved restoration of visual function. Experimental Eye Research, 86(1), 92-104. doi: 10.1016/j.exer.2007.09.012. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/5928b701
ISSN: 0014-4835
Popis: The aim of this study was to evaluate the functional efficacy of retinal progenitor cell (RPC) containing sheets with BDNF microspheres following subretinal transplantation in a rat model of retinal degeneration. Sheets of E19 RPCs derived from human placental alkaline phosphatase (hPAP) expressing transgenic rats were coated with poly-lactide-co-glycolide (PLGA) microspheres containing brain-derived neurotrophic factor (BDNF) and transplanted into the subretinal space of S334ter line 3 rhodopsin retinal degenerate rats. Controls received transplants without BDNF or BDNF microspheres alone. Visual function was monitored using optokinetic head-tracking behavior. Visually evoked responses to varying light intensities were recorded from the superior colliculus (SC) by electrophysiology at 60 days after surgery. Frozen sections were studied by immunohistochemistry for photoreceptor and synaptic markers. Visual head tracking was significantly improved in rats that received BDNF-coated RPC sheets. Relatively more BDNF-treated transplanted rats (80%) compared to non-BDNF transplants (57%) responded to a "low light" intensity of 1 cd/m2in a confined SC area. With bright light, the onset latency of SC responses was restored to a nearly normal level in BDNF-treated transplants. No significant improvement was observed in the BDNF-only and no surgery transgenic control rats. The bipolar synaptic markers mGluR6 and PSD-95 showed normal distribution in transplants and abnormal distribution of the host retina, both with or without BDNF treatment. Red-green cones were significantly reduced in the host retina overlying the transplant in the BDNF-treated group. In summary, BDNF coating improved the functional efficacy of RPC grafts. The mechanism of the BDNF effects-either promoting functional integration between the transplant and the host retina and/or synergistic action with other putative humoral factors released by the RPCs-still needs to be elucidated. © 2007 Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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