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  • Inflammatory cells proliferate in the choroid and retina without choroidal thickness change in early Type 1 diabetes
    Publication . Campos, António; Campos, Elisa J.; Martins, João; Rodrigues, Flávia S.C.; Silva, Rufino; Ambrósio, António Francisco
    Increasing evidence points to inflammation as a key factor in the pathogenesis of diabetic retinopathy (DR). Choroidal inflammatory changes in diabetes have been reported and in vivo choroidal thickness (CT) has been searched as a marker of retinopathy with contradictory results. We aimed to investigate the early stages in the retina and choroid in an animal model of Type 1 diabetes. Type 1 diabetes was induced in male Wistar rats via a single i.p. streptozotocin injection. At 8 weeks after disease onset, CT, choroidal vascular density, VEGF and VEGFR2 expression, microglial cell and pericyte distribution were evaluated. Diabetic rats showed no significant change in CT and choroidal vascular density. A widened pericyte-free gap between the retinal pigment epithelium and the choroid was observed in diabetic rats. The immunoreactivity of VEGFR2 was decreased in the retina of diabetic rats, despite no statistically significant difference in the immunoreactivity of VEGF. The density of microglial cells significantly increased in the choroid and retina of diabetic rats. Reactive microglial cells were found to be more abundant in the choroid of diabetic rats. Evidences of the interconnection between the superficial, intermediate, and deep plexuses of the retina were also observed. At early stages, Type 1 diabetes does not affect choroidal thickness and choroidal vascular density. Proliferation and reactivity of microglial cells occurs in the choroidal stroma and the retina. The expression of VEGFR2 decreases in the retina.
    2020-08-22Journal article Restricted access Show more
  • Bio-inspired polymeric iron-doped hydroxyapatite microspheres as a tunable carrier of rhBMP-2
    Publication . Patrício, Tatiana Marisa Fernandes; Mumcuoglu, Didem; Montesi, Monica; Panseri, Silvia; Witte-Bouma, Janneke; Garcia, Shorouk Fahmy; Sandri, Monica; Tampieri, Anna; Farrell, Eric; Sprio, Simone
    Hybrid superparamagnetic microspheres with bone-like composition, previously developed by a bio-inspired assembling/mineralization process, are evaluated for their ability to uptake and deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in therapeutically-relevant doses along with prolonged release pro- files. The comparison with hybrid non-magnetic and with non-mineralized microspheres highlights the role of nanocrystalline, nanosize mineral phases when they exhibit surface charged groups enabling the chemical linking with the growth factor and thus moderating the release kinetics. All the microspheres show excellent osteogenic ability with human mesenchymal stem cells whereas the hybrid mineralized ones show a slow and sustained release of rhBMP-2 along 14 days of soaking into cell culture medium with substantially bioactive effect, as reported by assay with C2C12 BRE-Luc cell line. It is also shown that the release extent can be modulated by the application of pulsed electromagnetic field, thus showing the potential of remote controlling the bioactivity of the new micro-devices which is promising for future application of hybrid biomimetic mi- crospheres in precisely designed and personalized therapies.
    2020-08-22Journal article Open access Show more