4 research outputs found
Retinal degeneration rat model: a study on the structural and functional changes in the retina following injection of sodium iodate
Retinal disorders account for a large proportion of ocular disorders that can lead to visual impairment or blindness, and yet our limited knowledge in the pathogenesis and choice of appropriate animal models for new treatment modalities may contribute to ineffective therapies. Although genetic in vivo models are favored, the variable expressivity and penetrance of these heterogeneous disorders can cause difficulties in assessing potential treatments against retinal degeneration. Hence, an attractive alternative is to develop a chemically-induced model that is both cost-friendly and standardizable. Sodium iodate is an oxidative chemical that is used to simulate late stage retinitis pigmentosa and age-related macular degeneration. In this study, retinal degeneration was induced through systemic administration of sodium iodate (NaIO3) at varying doses up to 80 mg/kg in Sprague-Dawley rats. An analysis on the visual response of the rats by electroretinography (ERG) showed a decrease in photoreceptor function with NaIO3 administration at a dose of 40 mg/kg or greater. The results correlated with the TUNEL assay, which revealed signs of DNA damage throughout the retina. Histomorphological analysis also revealed extensive structural lesions throughout the outer retina and parts of the inner retina. Our results provided a detailed view of NaIO3-induced retinal degeneration, and showed that the administration of 40 mg/kg NaIO3 was sufficient to generate disturbances in retinal function. The pathological findings in this model reveal a degenerating retina, and can be further utilized to develop effective therapies for RPE, photoreceptor, and bipolar cell regeneration
Dental pulp stem cells therapy overcome photoreceptor cell death and protects the retina in a rat model of sodium iodate-induced retinal degeneration
Blindness and vision loss contribute to irreversible retinal degeneration, and cellular therapy for retinal cell replacement has the potential to treat individuals who have lost light sensitive photoreceptors in the retina. Retinal cells are well characterized in function, and are a subject of interest in cellular replacement therapy of photoreceptors and the retinal pigment epithelium. However, retinal cell transplantation is limited by various factors, including the choice of potential stem cell source that can show variability in plasticity as well as host tissue integration. Dental pulp is one such source that contains an abundance of stem cells. In this study we used dental pulp-derived mesenchymal stem cells (DPSCs) to mitigate sodium iodate (NaIO3) insult in a rat model of retinal degeneration. Sprague-Dawley rats were first given an intravitreal injection of 3 × 105 DPSCs as well as a single systemic administration of NaIO3 (40 mg/kg). Electroretinography (ERG) was performed for the next two months and was followed-up by histological analysis. The ERG recordings showed protection of DPSC-treated retinas within 4 weeks, which was statistically significant (* P ≤ .05) compared to the control. Retinal thickness of the control was also found to be thinner (*** P ≤ .001). The DPSCs were found integrated in the photoreceptor layer through immunohistochemical staining. Our findings showed that DPSCs have the potential to moderate retinal degeneration. In conclusion, DPSCs are a potential source of stem cells in the field of eye stem cell therapy due to its protective effects against retinal degeneration
High EZH2 Protein Expression Is a Poor Prognostic Predictor in IDH1 R132H-Negative Gliomas
Accumulating data indicates that enhancer of zeste homology 2 (EZH2) and isocitrate dehydrogenase 1 (IDH1) are implicated in promoting tumourigenesis in a myriad of malignancies including gliomas. We aimed to determine the immunoexpression of EZH2 in gliomas and its correlation with clinicopathological variables. The prognostic value of the combined immunoexpression of EZH2 and IDH1 was further explored in a retrospective analysis involving 56 patients with histologically confirmed gliomas in Universiti Kebangsaan Malaysia Medical Centre from 2010 to 2016. The patients were then followed up for a period of five years. EZH2 and IDH1 R132H immunoexpressions were performed and analysed on respective tissue blocks. Five-year progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan–Meier analysis. Univariate and multivariate Cox proportional hazard regression models were performed to evaluate the value of EZH2 as an independent factor for the prediction of PFS and OS. High EZH2 immunoexpression was demonstrated in 27 (48.2%) gliomas. High EZH2 expression was significantly correlated with older age (p = 0.003), higher tumour grade (p < 0.001), negative IDH1 R132H immunoexpression (p = 0.039), a poor 5-year PFS (mean = 9.7 months, p < 0.001) and 5-year OS (mean = 28.2 months, p = 0.007). In IDH1 R132H-negative gliomas, there was a trend toward shorter 5-year PFS (mean = 8.0 months, p = 0.001) and 5-year OS (mean = 28.7 months, p = 0.06) in gliomas demonstrating high EZH2 expression compared with those with low EZH2 expression. High EZH2 immunoexpression is an unfavourable independent prognostic predictor of poor survival in gliomas. EZH2 analysis might therefore be of clinical value for risk stratification, especially in patients with IDH1 R132H-negative gliomas