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Yuhong Dong, Kevin Harkin, Laurence Feraille, Mei Chen, Heping Xu; SBC003 demonstrates neuroprotective effects in a murine model of N-nitroso-N-methylurea (NMU) induced photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2475.
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© ARVO (1962-2015); The Authors (2016-present)
SBC003, a novel small molecule, exhibits neuroprotective and neurorescuing effects in multiple in vitro neurodegenerative models. The purpose of the study is to investigate the neuroprotective effect of SBC003 in a mouse model with N-nitroso-N-methylurea (NMU) induced photoreceptor degeneration.
Eighteen 8-12-week-old female C57BL/6J mice were randomized into three groups: 1) NMU+vehicle; 2) NMU+ SBC003 20 mg/kg; 3) NMU+SBC003 50 mg/kg. NMU at a dose of 50 mg/kg was injected i.p. to all mice; SBC003 (or vehicle) was administered daily via oral gavage starting 3 days before NMU and continuing until 7 days after NMU challenge. Retina were imaged by spectral domain optical coherence tomography (OCT) 5 days before NMU and 7 days after NMU. All eyes were collected and processed for histological hematoxylin and eosin (H&E) staining. The thicknesses of photoreceptors was measured from different locations on OCT images and H&E slides, respectively. Photoreceptor thickness on H&E slides were quantified using automated Leica software (Leica, Heerbrugg), operated by a single masked observer. Results were expressed as the outer nuclear layer (ONL) area under the curve (AUC-1.75 to +1.75 µm) and number of rows of photoreceptor nuclei.
Histological analysis showed that the AUC under the ONL was significantly increased in SBC003 treated groups vs vehicle control, i.e. 83.08±19.05 in 50 mg/kg (p<0.001), 73.58±14.45 in 20 mg/kg (p<0.01) and 43.46±29.86 in vehicle control. The number of rows of photoreceptor nuclei was significantly increased in SBC003 treated groups vs vehicle control across all regions from central to peripheral, e.g. in mid-peripheral region 7.0±1.7 in 50 mg/kg (p<0.001), 6.4±1.2 in 20 mg/kg (p<0.01) vs 3.8±2.5 in vehicle control. In vivo OCT images showed increased thickness of photoreceptor layers vs control; and neuroretinal thickness in 50 mg/kg SBC003 group was significantly increased in peripheral (p<0.05), mid-peripheral (p<0.05) and central retina (p<0.01) vs vehicle control.
SBC003 exhibits a potent dose-dependent neuroprotective effect against NMU-induced retina degeneration. SBC003 is a promising therapeutic candidate for future development for human retinal degenerative diseases such as retinitis pigmentosa.
This is a 2020 ARVO Annual Meeting abstract.
ONL loss in vehicle control group at 7 days post NMU
ONL protected with SBC003 50mg/kg treatment at 7 days post NMU
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