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Long-term neuroprotective effects of NT-4-engineered mesenchymal stem cells injected intravitreally in a mouse model of acute retinal injury

Session Details

Session Title: New Drug Treatment

Session Date/Time: Saturday 13/09/2014 | 14:30-16:30

Paper Time: 15:34

Venue: Boulevard F

First Author: : A.Machalińska POLAND

Co Author(s): :    B. Machaliński   A. Józkowicz   J. Dulak        

Abstract Details

Purpose:

Retinal degenerative diseases targeting the retinal pigment epithelium (RPE) and adjacent photoreceptors affect millions of people worldwide. The field of stem cell- and gene-based therapy holds great potential for the treatment of such diseases. The present study sought to graft genetically engineered mesenchymal stem cells (MSCs) that continuously produce neurotrophin-4 (NT-4) into the murine eye after the onset of acute retinal injury.

Setting:

Pomeranian Medical University, Al. Powstancow Wlkp. 72, 70-111 Szczecin, Poland Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Gronostajowa 7, 30-387 Krakow, Poland

Methods:

C57BL/6 mice were subjected to acute retinal damage using a low dose of sodium iodate (20 mg/kg of body weight), followed by intravitreal injection of lentivirally modified MSCs-NT-4 into the right eye. At 3 months after the MSC transplantation grafted cell survival, retinal function and gene expression were analyzed.

Results:

Immunofluorescence analysis confirmed that transplanted MSCs survived for at least 3 months after intravitreal injection and preferentially migrated towards sites of injury within the retina. MSC-NT-4 actively produced NT-4 in the injured retina and significantly protected damaged retinal cells, as evaluated by electroretinography (ERG) and optical coherence tomography (OCT). Importantly, the long-term therapy with MSCs-NT-4 was also associated with induction of prosurvival signaling, considerable overexpression of some subsets of transcripts, including several members of the crystallin β-γ superfamily (Cryba4, Crybb3, Cryba2, Crybb1, Crybb2, Cryba1, Crygc) and significant upregulation of biological processes associated with visual perception, sensory perception of light stimulus, eye development, sensory organ development, and system development.

Conclusions:

Transplantation of genetically modified MSCs that produce neurotrophic growth factors may represent a useful strategy for treatment of different forms of retinopathies in the future.

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