Bone Marrow-Derived Mononuclear Cell Transplants Decrease Retinal Gliosis in Two Animal Models of Inherited Photoreceptor Degeneration

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.

Drinking hydrogen water improves photoreceptor structure and function in retinal degeneration 6 mice

“…In P23H-1 and Royal College of Surgeons (RCS) rats as other animal models, administration of basic fibroblast growth factor (FGF2) and minocycline has been shown to increase photoreceptor survival. Minocycline reduced microglial activation and migration, and the combination of FGF2 and minocycline exhibited greater neuroprotective effects than the effects of either agent alone 42 . The therapeutic effects of combined administration of hydrogen and treatments with different mechanisms of action clearly merits further research.…”

Glial Cell Activation and Oxidative Stress in Retinal Degeneration Induced by β-Alanine Caused Taurine Depletion and Light Exposure

“…All sections were subjected to a double immunohistofluorescence protocol following previously described procedures [ 20 , 28 , 38 , 50 ]. First, the sections were permeabilized by washing them in PBS + 0.5% Triton X-100 and then incubated overnight at 4 °C with a mixture of the primary antibodies (see next paragraph) diluted in blocking buffer solution (PBS, 2% Triton X-100, and 2% normal donkey serum; NDS, Jackson Immuno Research, Inc., Cambridge, UK).…”

“…In RCS rats, photoreceptor degeneration courses with microglial cell activation and GFAP over-expression in Müller cells [ 19 , 20 , 27 ]. Moreover, micro and macroglial cell reaction are common features of inherited [ 19 , 20 , 28 , 29 , 30 , 31 ] and light-induced [ 21 , 32 ] photoreceptor degenerations [ 27 , 33 ]. This glial reactivity during photoreceptor degeneration may be related to retinal remodeling and be harmful to the retina [ 21 , 27 , 33 ].…”

Intravitreal and subretinal syngeneic bone marrow mononuclear stem cell transplantation improves photoreceptor survival but does not ameliorate retinal function in two rat models of retinal degeneration

“…2017; Di Pierdomenico et al . 2020a). Because up to now the survival of the cells has been limited, it has been proposed that these beneficial effects are due to a paracrine trophic effect achieved through their sustained release of neurotrophic, anti‐angiogenic and immunomodulatory factors (Park et al .…”

“…Moreover, it has been documented that these transplants decrease retinal inflammation (Di Pierdomenico et al . 2020a) and this immunosuppressive effect may be also beneficial, as inflammation plays a role in RP and AMD (Tzameret et al . 2014; Tzameret et al .…”