RESUMEN
Previously, we developed a simple procedure of intracameral injection of silicone oil (SO) into mouse eyes and established the mouse SOHU (SO-induced ocular hypertension under-detected) glaucoma model with reversible intraocular pressure (IOP) elevation and significant glaucomatous neurodegeneration. Because the anatomy of the non-human primate (NHP) visual system closely resembles that of humans, it is the most likely to predict human responses to diseases and therapies. Here we tried to replicate the mouse SOHU glaucoma model in rhesus macaque monkeys. All six animals that we tested showed significant retinal ganglion cell (RGC) death, optic nerve (ON) degeneration, and visual functional deficits at both 3 and 6 months. In contrast to the mouse SOHU model, however, IOP changed dynamically in these animals, probably due to individual differences in ciliary body tolerance capability. Further optimization of this model is needed to achieve consistent IOP elevation without permanent damage of the ciliary body. The current form of the NHP SOHU model recapitulates the severe degeneration of acute human glaucoma, and is therefore suitable for assessing experimental therapies for neuroprotection and regeneration, and therefore for translating relevant findings into novel and effective treatments for patients with glaucoma and other neurodegenerations.
Asunto(s)
Glaucoma , Hipertensión Ocular , Humanos , Ratones , Animales , Macaca mulatta , Aceites de Silicona , Glaucoma/metabolismo , Hipertensión Ocular/inducido químicamente , Hipertensión Ocular/metabolismo , Presión Intraocular , Modelos Animales de EnfermedadRESUMEN
Multiwalled carbon nanotubes (MWCNT) were homogeneously covered with a bio-functional polydopamine (PDOP) by a simple dip-coating approach in mild basic solution. Then, uniformly dispersed and highly loaded platinum nanoparticles (PtNPs) were deposited on MWCNT@PDOP by a mild reductant, and were characterized by transmission electron microscopy and x-ray photoelectron spectroscopy. Afterwards, this nanocomposite was modified on the glass carbon electrode and applied to simultaneously determine dopamine (DA) and uric acid (UA) by differential pulse voltammetry (DPV). Results showed that a linear electro-oxidation response was found for DA and UA in the range of 0.25-20 µM and 0.3-13 µM with the detection limit (S/N = 3) of 0.08 µM and 0.12 µM, respectively. In addition, the detection sensitivities for DA and UA by DPV were 1.03 µA µM(-1) and 2.09 µA µM(-1), respectively, which were much higher than those from a cyclic voltammogram. Finally, the reproducibility and stability of the nanocomposite were also evaluated, demonstrating that such MWCNT@PDOP@PtNPs can be a promising candidate for advanced electrode material in electrochemical sensing and other electrocatalytic applications.
Asunto(s)
Dopamina/análisis , Técnicas Electroquímicas/métodos , Indoles/química , Nanopartículas del Metal/química , Nanotubos de Carbono/química , Platino (Metal)/química , Polímeros/química , Ácido Úrico/análisis , Electrodos , Límite de Detección , Nanopartículas del Metal/ultraestructura , Nanotubos de Carbono/ultraestructuraRESUMEN
Recently, we established silicone oil-induced ocular hypertension (SOHU) mouse model with significant glaucomatous neurodegeneration. Here we characterize two additional variations of this model that simulate two distinct glaucoma types. The first is a chronic model produced by high frequency (HF) pupillary dilation after SO-induced pupillary block, which shows sustained moderate IOP elevation and corresponding slow, mild glaucomatous neurodegeneration. We also demonstrate that although SO removal quickly returns IOP to normal, the glaucomatous neurodegeneration continues to advance to a similar degree as in the HF group without SO removal. The second, an acute model created by no pupillary dilation (ND), shows a greatly elevated IOP and severe inner retina degeneration at an early time point. Therefore, by a straightforward dilation scheme, we extend our original SOHU model to recapitulate phenotypes of two major glaucoma forms, which will be invaluable for selecting neuroprotectants and elucidating their molecular mechanisms.
Asunto(s)
Modelos Animales de Enfermedad , Glaucoma/patología , Hipertensión Ocular/fisiopatología , Degeneración Retiniana/patología , Células Ganglionares de la Retina/patología , Aceites de Silicona/toxicidad , Enfermedad Aguda , Animales , Femenino , Glaucoma/inducido químicamente , Presión Intraocular , Masculino , Ratones , Ratones Endogámicos C57BL , Hipertensión Ocular/inducido químicamente , Degeneración Retiniana/inducido químicamente , Células Ganglionares de la Retina/efectos de los fármacos , Aceites de Silicona/administración & dosificaciónRESUMEN
Understanding the molecular mechanism of glaucoma and development of neuroprotectants is significantly hindered by the lack of a reliable animal model that accurately recapitulates human glaucoma. Here, we sought to develop a mouse model for the secondary glaucoma that is often observed in humans after silicone oil (SO) blocks the pupil or migrates into the anterior chamber following vitreoretinal surgery. We observed significant intraocular pressure (IOP) elevation after intracameral injection of SO, and that SO removal allows IOP to return quickly to normal. This simple, inducible and reversible mouse ocular hypertension model shows dynamic changes of visual function that correlate with progressive retinal ganglion cell (RGC) loss and axon degeneration. It may be applicable with only minor modifications to a range of animal species in which it will generate stable, robust IOP elevation and significant neurodegeneration that will facilitate selection of neuroprotectants and investigating the pathogenesis of ocular hypertension-induced glaucoma.