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I.-H. Pang, H. Zeng, Y. Wang, D. L. Fleenor, M. B. Wax, A. F. Clark; Toxicity of Capsaicin Receptor TRPV1 Agonists on Cultured Adult Rat Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4943.
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The capsaicin receptor TRPV1, also known as the vanilloid receptor VR1, is a non-selective cation channel that responds to chemical and physical stimuli. It is present in sensory neurons as well as regions of the brain that are susceptible to neurodegenerative insults. Prolonged TRPV1 activation induces cation influx, mitochondrial dysfunction, and eventually neuronal cell death. To evaluate its potential toxic effect in the retinal ganglion cell (RGC), we assessed distribution of TRPV1 in the rat retina and tested effects of TPRV1 agonists on survival of cultured RGC.
Immunohistochemistry was used to localize TRPV1 in cross sections of the rat retina. Freshly isolated adult rat retinal cells were cultured with TRPV1 agonists and antagonist to assess toxicity. Viable RGCs were identified by positive Thy1 immunocytochemical staining.
TRPV1 immunoreactivity was present in most neurons of the ganglion cell layer and sporadically in the inner nuclear layer of rat retinas. TRPV1 agonists were cytotoxic to cultured RGCs in a concentration-dependent manner. At 100 nM, resiniferatoxin (Rftx), (E)-capsaicin, and (Z)-capsaicin induced a 34.5 ± 5.0% (mean ± SEM, n = 12; p < 0.05), 17.3 ± 6.3% (n = 6, p < 0.05), and 29.9 ± 2.7% (n = 6, p < 0.05) loss of RGCs, respectively. The cytotoxic effect of these compounds was blocked by treatment of a TRPV1 antagonist 6-iodo-nordihydrocapsaicin (6-IDHC). At 10 µM, 6-IDHC completely protected the RGC from the toxic effects of Rftx and capsaicin. The protective action of 6-IDHC was specific for TRPV1 cytotoxicity. It did not protect glutamate- or trophic factor withdrawal-induced cytotoxicity in these cells.
TRPV1 is expressed in the RGC. Although its function is not totally understood, future delineation of the biology of TRPV1-induced RGC death may shed light on the pathogenesis, and ultimately medical intervention of certain retinopathies, such as glaucoma.
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