Effects of a combinatorial treatment with gene and cell therapy on retinal ganglion cell survival and axonal outgrowth after optic nerve injury

Gabriel Nascimento-dos-Santos, Leandro Coelho Teixeira-Pinheiro, Almir Jordão da Silva-Júnior, Luiza Rachel Pinheiro de Carvalho, Louise Alessandra Mesentier-Louro, William W. Hauswirth, Rosalia Mendez-Otero, Marcelo Felippe Santiago, Hilda Petrs-Silva

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

After an injury, axons in the central nervous system do not regenerate over large distances and permanently lose their connections to the brain. Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury.

Original languageEnglish
Pages (from-to)27-39
Number of pages13
JournalGene Therapy
Volume27
Issue number1-2
DOIs
StatePublished - 1 Feb 2020
Externally publishedYes

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