Neuroprotective effects of the cannabinoid agonist HU210 on retinal degeneration

Cannabinoids have been demonstrated to exert neuroprotective effects on different types of neuronal insults. Here we have addressed the therapeutic potential of the synthetic cannabinoid HU210 on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model for autosomal dominant retinitis pigmentosa (RP). In P23H rats administered with HU210 (100 μg/kg, i.p.) from P24 to P90, ERG recordings showed an amelioration of vision loss, as compared to vehicle-administered animals. Under scotopic conditions, the maximum a-wave amplitudes recorded at P60 and P90 were higher in HU210-treated animals, as compared to the values obtained in untreated animals. The scotopic b-waves were significantly higher in treated animals than in untreated rats at P30, P60 and P90. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. HU210-treated animals had 40% more photoreceptors than untreated animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were also preserved in HU210-treated P23H rats. These results indicate that HU210 preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in P23H rats. These data suggest that cannabinoids are potentially useful to delay retinal degeneration in RP patients.

Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects

Background: Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Chronic microglia activation is associated with various neurodegenerative diseases including retinitis pigmentosa. The objective of this study was to quantify microglia activation in the retina of P23H rats, an animal model of retinitis pigmentosa, and to evaluate the therapeutic effects of TUDCA (tauroursodeoxycholic acid), which has been described as a neuroprotective compound. Methods: For this study, homozygous P23H line 3 and Sprague-Dawley (SD) rats were injected weekly with TUDCA (500 mg/kg, ip) or vehicle (saline) from 20 days to 4 months old. Vertical retinal sections and whole-mount retinas were immunostained for specific markers of microglial cells (anti-CD11b, anti-Iba1 and anti-MHC-II). Microglial cell morphology was analyzed and the number of retinal microglial was quantified. Results: Microglial cells in the SD rat retinas were arranged in regular mosaics homogenously distributed within the plexiform and ganglion cell layers. In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution. In addition, a large number of amoeboid CD11b-positive cells were observed in the P23H rat retina, even in the subretinal space. Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space. Conclusions: These results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.

The orchestration of modes and EFL audio-visual comprehension: A multimodal discourse analysis of vodcasts

This thesis explores the role of multimodality in language learners’ comprehension, and more specifically, the effects on students’ audio-visual comprehension when different orchestrations of modes appear in the visualization of vodcasts. Firstly, I describe the state of the art of its three main areas of concern, namely the evolution of meaning-making, Information and Communication Technology (ICT), and audio-visual comprehension. One of the most important contributions in the theoretical overview is the suggested integrative model of audio-visual comprehension, which attempts to explain how students process information received from different inputs. Secondly, I present a study based on the following research questions: ‘Which modes are orchestrated throughout the vodcasts?’, ‘Are there any multimodal ensembles that are more beneficial for students’ audio-visual comprehension?’, and ‘What are the students’ attitudes towards audio-visual (e.g., vodcasts) compared to traditional audio (e.g., audio tracks) comprehension activities?’. Along with these research questions, I have formulated two hypotheses: Audio-visual comprehension improves when there is a greater number of orchestrated modes, and students have a more positive attitude towards vodcasts than traditional audios when carrying out comprehension activities. The study includes a multimodal discourse analysis, audio-visual comprehension tests, and students’ questionnaires. The multimodal discourse analysis of two British Council’s language learning vodcasts, entitled English is GREAT and Camden Fashion, using ELAN as the multimodal annotation tool, shows that there are a variety of multimodal ensembles of two, three and four modes. The audio-visual comprehension tests were given to 40 Spanish students, learning English as a foreign language, after the visualization of vodcasts. These comprehension tests contain questions related to specific orchestrations of modes appearing in the vodcasts. The statistical analysis of the test results, using repeated-measures ANOVA, reveal that students obtain better audio-visual comprehension results when the multimodal ensembles are constituted by a greater number of orchestrated modes. Finally, the data compiled from the questionnaires, conclude that students have a more positive attitude towards vodcasts in comparison to traditional audio listenings. Results from the audio-visual comprehension tests and questionnaires prove the two hypotheses of this study.