Minocycline and bone marrow-derived mononuclear cells as potential therapeutics for hereditary retinal degenerations

Abstract

PURPOSE: To assess in Royal College of Surgeons (RCS) rats if the combination of two previously documented neuroprotective strategies: minocycline administration and bone marrow-derived mononuclear cells (BM-MNCs) intravitreal transplantation, offers enhanced neuroprotection compared with each treatment alone. METHODS: Forty-eight homozygous pigmented RCS rats were divided into four groups: control, intravitreal BM-MNC transplantation, systemic minocycline treatment or combined therapy. Treatments were administered at postnatal day (P) 27-28. Animals were evaluated in vivo by spectral domain optical coherence tomography (SD-OCT) at P28, P35 and P51. Retinal sections were analysed for photoreceptor survival (outer nuclear layer [ONL] cell counts), synaptic preservation (Bassoon immunoreactivity), microglial activation (Iba-1+ cells) and macroglial reactivity (glial fibrillary acidic protein [GFAP] expression). RESULTS: Both BM-MNC and minocycline monotherapies significantly preserved total and outer retinal thicknesses and increased ONL nuclei counts compared with controls. Combined treatment yielded superior protection at both P35 and P51. Minocycline alone or in combination significantly reduced microglial cell activation, while BM-MNCs alone or in combination significantly reduced GFAP expression. Synaptic integrity in the outer plexiform layer, assessed via Bassoon labelling, was significantly better preserved in treated animals, with the highest levels observed in the combined therapy group. CONCLUSIONS: Minocycline and BM-MNCs provide complementary neuroprotective effects in the RCS rat model. While minocycline reduces microglial activation, BM-MNCs modulate macroglial response. Their combination enhances photoreceptor survival and synaptic preservation more effectively than either treatment alone. These findings support the therapeutic potential of combining pharmacological and cell-based interventions in hereditary retinal degenerations.