Adjuvant stem cell-based therapy in acute retinal injury after sodium iodate administration in mice: Morphological and functional study

• Published in: Acta neurobiologiae experimentalis Vol. 73; no. 1; p. 182
• Main Authors: Machalinska, A, Roginska, D, Pius, E, Stepniewski, J, Kawa, M, Jozkowicz, A, Dulak, P, Machalinski, B
• Format: Journal Article
• Language: English
• Published: 01-01-2013
• Subjects: Lentivirus
• ISSN: 0065-1400

Ophthalmic diseases, especially retinal degeneration belong to prominent causes of disability in developed countries. Thus, special attention has been focused on research aimed on establishing new protocols of efficient stem cell (SC)-based therapy of these disorders. The aim of this study was to determine and optimize a new strategy of SC-based therapy of selectively damaged retina after sodium iodate (NaIO sub(3)) administration in C57BL/6J mice. First, we sought to assess the regenerative mechanisms triggered after acute chemical injury of retinal pigment epithelium and neurosensory retina induced by NaIO sub(3), in mice. The intravenous injection of NaIO sub(3) provides a useful model for the study of retinal degeneration since it mimics some retinal degenerative diseases in humans, e.g., gyrate atrophy, retinitis pigmentosa or age-related macular degeneration. We evaluated the kinetics of morphological and functional changes within mice retinas injured with NaIO sub(3) via: (1) morphological study; (2) evaluation of expression of selected neurotrophins (NTs) in injured retina; (3) visualization of proliferating and apoptotic cells; (4) electrophysiology. Our findings revealed that massive destruction of the tissue was associated with irreversible retinal dysfunction, whereas moderate retinal injury triggered regenerative mechanisms that restore bioelectrical function of the damaged retina. Next, we performed intravitreal transplantation of murine GFP+Lin- cells on the 1st day since NalO, administration. We analyzed number and localization of intravitreally injected GFP+Lin- cells within recipients' retinas as well as the retinal functional changes (electroretinography). By employing stem/progenitor cell-based therapy we achieved noticeable improvement in retinal function, particularly in the case of only partial primary destruction of retinal tissue. Furthermore we investigated the neuroprotective effects of different NTs, administered intravitreally via genetically modified SCs into degenerating retinal tissue. The synthetic viral vectors based on lentivirus (LVs) backbone was used to deliver NT genes into mesenchymal stem cells isolated from bone marrow. Then, we conducted multipart analysis based on functional tests, e.g., electroretinography as well as histological, immu-nohistochemical, morphometric, and molecular biology studies. We found that specific, exogenously administered NTs, such as NT4/5 could effectively stimulate photoreceptor survival in the degenerating retinas. Our findings reveal that the proposed therapeutic strategy could be recommended as adjuvant therapy supporting endogenous regeneration of acute retinal damage. However, further more extensive studies are needed before the introduction of this kind of therapy into patients.