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Johnny Di Pierdomenico, Diego Garcia-Ayuso, Marta Agudo-Barriuso, Manuel Vidal-Sanz, Maria Paz Villegas-Perez; Differential and additive effects of bFGF and minocycline in two animal models of inherited retinal degeneration.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4549.
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© ARVO (1962-2015); The Authors (2016-present)
To analyze during the period of rapid photoreceptor death the neuroprotective effects of different neurotrophic factors and minocycline and the role of microglia in two animal models of inherited retinal degeneration with different mechanisms of degeneration.
Homozygous albino P23H-1 (P10) and pigmented Royal College of Surgeons (RCS; P33) rats received one intravitreal injection (IVI) of different neurotrophic factors (CNTF, bFGF or PEDF) or continuous treatment with intraperitoneal (IP) minocycline or a combination of both (IVI of bFGF and IP minocycline). At P21 (P23H-1) or P45 (RCS) the retinas were cross sectioned, immunoreacted with antibodies against S or L/M opsins, rhodopsin or Iba1 and counterstained with DAPI. In automatic photographic reconstructions (20x) of three retinal sections per animal (2 animals per group), retinal morphology was assessed qualitatively. Also, the number of nuclei rows in the outer nuclear layer (ONL) and of microglial cells in each retinal layer was quantified manually in eight standard areas per retinal section.
In both models, CNTF and PEDF had no effects, but bFGF and minocycline increased significantly and in similar proportions photoreceptor survival. Also, the combination of minocycline+bFGF had additive effects in both models. The numbers of microglial cells in the different retinal layers were similar to those observed in dystrophic age-matched animals and remained stable after trophic factor administration. However, the numbers of microglial cells were higher in the GCL and lower in the ONL and OS layer after minocycline treatment, indicating that this antibiotic decreased microglial migration from the inner to the outer retinal layers.
In both models of retinal degeneration bFGF and minocycline showed neuroprotective effects that were additive. The mechanism of protection may thus be different for both substances and for minocycline it may be mediated by microglial inhibition.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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