CONTRATADOS
GIRARDI Elena Silvia
congresos y reuniones científicas
Título:
Retinal Neuroprotective effects of A2a receptor antagonist SCH 58261
Autor/es:
MANUEL SOLIÑO¹, ; ESTER LÓPEZ², LEONARDO JUAREZ², NOELÍ MARTIGNONE², MARIANA BAREIRO², ELENA GIRARDI², JUAN LÓPEZ-COSTA; ELENA GIRARDI ; JUAN LÓPEZ-COSTA1,2
Lugar:
Toronto
Reunión:
Congreso; 10th Annual Canadian Neuroscience Meeting; 2016
Institución organizadora:
Canadian Association for Neuroscience
Resumen:
Retinal Neuroprotective effects of A2a receptor antagonist SCH 58261Light induced retinal degeneration (LIRD) resembles retinal degenerative diseases and is a useful model to search for neuroprotective strategies. The modulation of adenosine A2a receptors has proved to be neuroprotective in ischemic and excitotoxic retinal injury, and in diverse CNS pathologies. The aim of this work was to evaluate the potential neuroprotective effect of A2a antagonists. We have quantified its effects on Müller cell (MC) activation and on the apoptotic levels using the model of LIRD. Presently we are also measuring the shifts on adenosine receptors to gain further insight of the involvement of the adenosine mediated transmission in the model.Sprague Dawley rats were intravitreally injected in one eye with SCH 58261. Contralateral eyes were injected with vehicle as control. Then, rats were submitted to either continuous illumination (12000 lux) or the housing?s regular illumination cicle (12hs:12hs; 80lux) during 1 day. Eyes were processed either for histological or biochemical studies. The sections were processed by immunocytochemistry (ICC) or TUNEL. Retinal homogenates were processed by western blot (WB). Primary antibodies against GFAP (rabbit polyclonal, DAKO), activated caspase 3 (C3a; rabbit polyclonal, Sigma).GFAP immunoreactive areas, number of positive TUNEL cells and receptor immunoreactivity (IR) were quantified using Fiji image analysis software. Western blot results were measured using Image Lite Studio software. Data were statistically analysed using Student´s t test. Animals treated with SCH 58261 showed a diminution in GFAP expression confirmed by WB and ICC (P< 0.01 and P=0.0001; respectively). C3a levels measured by WB are showing a trend indicating a lower expression in the treated eyes, TUNEL results still require further analysis. Our results suggest that the activation of MCs is controlled at least partially by adenosine mediated transmission. A2a antagonism has shown to have diminished glial reactivity in our model. As MCs have pro and antiapoptotic effects, we sustain that adenosine receptor modulation is a plausible therapeutic strategy. Additionally, our current results show a lower level of apoptosis that needs further confirmation in the following weeks. Globally, SCH 58261 seems to have a neuroprotective effect in the CI model supporting the idea that this therapeutic strategy should be better studied as a possible way to reach effective therapeutics in neurodegenerative diseases.
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