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C. L. Luna, A. Sesto, M. C. Acosta, M. C. Jiménez, J. Gallar, C. Belmonte, A. I. Jiménez; TRPV1 siRNA Topical Treatment Reduces the Response to Ocular Surface Irritation With Capsaicin. Invest. Ophthalmol. Vis. Sci. 2007;48(13):373.
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To test that TRPV1 expression in sensory nerve terminals is reduced by topical administration of a siRNA that silences the gene coding the capsaicin receptor TRPV1, thereby decreasing chemical sensitivity of polymodal nociceptors of the cornea.
Three different siRNA were designed according to the parameters of the predictive software SIRFINDER. These siRNAs are homologous for guinea pig and human TRPV1 gene. The irritative behavioural response elicited by a 10µL drop of capsaicin (100µM) applied daily to both eyes during 5-10 days period was measured in adult male guinea pigs. The number of scratching and wiping movements directed to the eye, the tearing volume and the degree of conjunctival hyperemia were assessed during 5 min period after capsaicin application. During the first 3 days, a solution containing one of the siRNAs was applied daily to the right eye while the left eye was treated with saline.
Treatment with different siRNAs elicited in the right eye a gradual reduction in the number of scratching/wiping movements evoked by capsaicin while the response to capsaicin in the saline-treated eye was not modified. Tearing and conjunctival hyperemia evoked by capsaicin were unaffected by siRNA treatment.
Reduced expression of TRPV1 receptor in the cornea obtained by topical administration of siRNA specifically directed the downregulation expression level of the TRPV1 gene appears to decrease the behavioural response to ocular surface irritation evoked by ocular capsaicin. Capsaicin activates corneal polymodal nerve terminals that express TRPV1 channels. These channels are involved in the nerve impulse responses to exogenous and endogenous substances mediating inflammation and pain. It is conceivable that a reduced activation of polymodal nociceptor fibers secondary to a low expression of TRPV1 receptor, is the cause of the attenuated behavioural response to corneal irritation by capsaicin. Thus, TRPV1 silencing may be an useful therapy to treat ocular inflammatory pain.
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