Abstract
Inherited photoreceptor degenerations are not treatable diseases and a frequent cause of blindness in working ages. In this study we investigate the safety, integration and possible rescue effects of intravitreal and subretinal transplantation of adult human bone-marrow-derived mononuclear stem cells (hBM-MSCs) in two animal models of inherited photoreceptor degeneration, the P23H-1 and the Royal College of Surgeons (RCS) rat. Immunosuppression was started one day before the injection and continued through the study. The hBM-MSCs were injected in the left eyes and the animals were processed 7, 15, 30 or 60 days later. The retinas were cross-sectioned, and L- and S- cones, microglia, astrocytes and Müller cells were immunodetected. Transplantations had no local adverse effects and the CD45+ cells remained for up to 15 days forming clusters in the vitreous and/or a 2–3-cells-thick layer in the subretinal space after intravitreal or subretinal injections, respectively. We did not observe increased photoreceptor survival nor decreased microglial cell numbers in the injected left eyes. However, the injected eyes showed decreased GFAP immunoreactivity. We conclude that intravitreal or subretinal injection of hBM-MSCs in dystrophic P23H-1 and RCS rats causes a decrease in retinal gliosis but does not have photoreceptor neuroprotective effects, at least in the short term. However, this treatment may have a potential therapeutic effect that merits further investigation.
Highlights
Photoreceptor degenerative diseases can be inherited or acquired and be caused by genetic abnormalities or other less well-known nutritional or environmental factors [1,2]
The most frequent inherited retinal degeneration is retinitis pigmentosa (RP), that has a prevalence of around 1 in 4000 individuals [7] and comprises a group of different diseases caused by mutations in more than 300 genes and loci [7,8,9]
Graphs show the mean numbers ± SD of nuclei rows in the outer nuclear layer (ONL) of control Pievald Viro Glaxo (PVG) rats and in the right uninjected and left eyes of Royal College of Surgeons (RCS) rats that received intravitreal injections (IVI) (K) or subretinal injections (SRI) (L) of hBM-MSCs
Summary
Photoreceptor degenerative diseases can be inherited or acquired and be caused by genetic abnormalities or other less well-known nutritional or environmental factors [1,2]. These diseases are at present, the first cause of irreversible blindness in developed countries and one of the leading causes of irreversible blindness in the world [3,4,5,6]. It is believed that there are more yet-unidentified mutations [7,8,9]. Why cones die following rods in RP is still a matter of consideration [12,13,14,15]
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