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Vicente Bermudez, Angela Suburo; The endothelin receptor A (ETA) would be involved in the intrarretinal transmission of visual stimuli. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2491.
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We have previously shown the presence of ETA in photoreceptor synaptic terminals (Torbidoni et al., 2005; 2006). Also, under a phototoxic environment, blocking ETA with clazosentan increases photoreceptor loss (Bermúdez et al., 2012). To investigate the possible role of ETA in the transmission of visual stimuli we have now studied: (a) the effects of clazosentan on ETA and the synaptic protein PSD95 immunoreactivities; (b) the activation of c-fos after exposure to physiological luminous stimuli.
Male Balb-c mice (5-7 weeks old), cared according to the ARVO Statement for the use of animals, were exposed to phototoxic stimuli (1500 lux) for 2 days (n = 3 per group) or to non-phototoxic stimuli (0.3 lux at 2 Hz) for 60 min. Animals received saline solution or clazosentan (10 mg/kg/day). Enucleation was done under anesthesia and eyes were processed for immunohistochemical detection of ETA, synaptic protein PSD95, or c-fos.
After phototoxic exposure, ETA-IR in the outer plexiform layer (OPL) was lower in animals treated with clazosentan than in saline controls. PSD95-IR, by contrast, was higher in clazosentan-treated mice than in the corresponding controls. c-fos+ nuclei were absent in the retina of control animals kept in the dark. After stroboscopic stimuli, c-fos appeared in the inner nuclear layer (INL) and the ganglion cell layer (GCL). Mice treated with clazosentan showed higher numbers of c-fos+ nuclei than controls.
The PSD95-IR increase and the ETA decrease observed after clazosentan treatment suggest that pharmacological inhibition of the ETA receptor induced structural changes of photoreceptor presynaptic structures. Since these modifications may be associated with the modulation of synaptic transmission in the outer retina, we evaluated the activation of c-fos in nuclei of the inner retina after physiological stimulation. The number of c-fos+ nuclei in the INL, which reflects activation of the OPL, was higher in clazosentan treated animals than in controls. Taking all into account, we postulate that ETA receptors might modulate photoreceptor transmission at the OPL.
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