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Melissa Kaye Jones, Bin Lu, Mehrnoosh Saghizadeh, Neil Bhowmick, Clive Svendsen, Shaomei Wang; Gene and protein expression changes following human neural progenitor cell injection into a retinal degeneration rodent model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3599.
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© ARVO (1962-2015); The Authors (2016-present)
Stem and progenitor cell transplantation provides therapeutic promise for treating degenerative retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Our previous studies have shown that a subretinal injection of human neural progenitor cells (hNPCs) into the Royal College of Surgeons (RCS) rats with inherited retinal degeneration preserved both visual function and photoreceptors. The modes of action of stem cell-based therapies and the response of the host retina to injected stem and progenitor cells are largely unknown. The purpose of this study was to identify some of the hNPC-induced expression changes in a model of retinal degeneration that aid in visual preservation and photoreceptor survival.
hNPCs were subretinally injected into RCS rats at an early stage of degeneration under immunosuppression. Visual function was examined by optokinetic response (OKR). Rat retinal tissue was collected for examination of gene and protein expression. RNA sequencing (RNA-seq) transcriptome analyses were conducted and transcriptional expression was validated by qPCR. Further confirmation was performed by protein analyses.
A single subretinal injection of hNPCs into RCS rats at early stages of degeneration significantly preserved both photoreceptors and visual function, as compared with sham and untreated control animals. Trascriptome changes in the RCS rat were detected following injection of hNPCs. Immunohistochemical analyses revealed that hNPCs increased expression of TGF-β signaling factors in RCS rats.
Human neural progenitor cells (hNPCs) offered preservation of vision after a single subretinal injection into a well-established rodent model of retinal degeneration. Changes in gene expression following injection of hNPCs may aid in preserving both visual function and photoreceptors. The TGF-β signaling pathway may be affected in retinal degeneration, and is aided with injection of hNPCs. By understanding the interaction between hNPCs and the retina, future stem cell treatments for retinal degenerative diseases could be enhanced for greater efficacy.
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