Long-Term Neuroprotective Effects of NT-4-Engineered Mesenchymal Stem Cells Injected Intravitreally in a Mouse Model of Acute Retinal Injury

Anna Machalinska, Milosz Piotr Kawa, Ewa Pius-Sadowska, Jacek Stepniewski, Witold Nowak, Dorota Roginska, Katarzyna Kaczynska, Bartlomiej Baumert, Barbara Wiszniewska, Alicja Jozkowicz, Jozef Dulak, Boguslaw Machalinski*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Retinal degenerative diseases targeting the 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.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 MSC-NT-4 into the right eye. At 3 months after the MSC transplantation grafted cell survival, retinal function and gene expression were analyzed.Immunofluorescence analysis confirmed that transplanted MSCs survived for at least 3 months after intravitreal injection and preferentially migrated toward 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 ERG and optical coherence tomography (OCT). Of importance, the long-term therapy with MSC-NT-4 was also associated with induction of prosurvival signaling, considerable overexpression of some subsets of transcripts, including several members of the crystallin ?-? superfamily (Cryba4, Crybb3, Cryba2, Crybb1, Crybb2, Cryba1, and Crygc) and significant upregulation of biological processes associated with visual perception, sensory perception of light stimulus, eye development, sensory organ development, and system development.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.
Original languageEnglish
Pages (from-to)8292-8305
JournalInvestigative Ophthalmology & Visual Science
Volume54
Issue number13
DOIs
Publication statusPublished - Dec 2013

Keywords

  • electroretinography
  • gene expression
  • gene therapy
  • MSCs
  • neurotrophin-4
  • retinal injury
  • sodium iodate

Fingerprint

Dive into the research topics of 'Long-Term Neuroprotective Effects of NT-4-Engineered Mesenchymal Stem Cells Injected Intravitreally in a Mouse Model of Acute Retinal Injury'. Together they form a unique fingerprint.

Cite this