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Editors Selection IGR 8-2

Basic Reseach: ET receptors

Comment by Thomas Yorio on:

12474 Pharmacological and functional characterization of endothelin receptors in bovine trabecular meshwork and ciliary muscle, Choritz L; Rosenthal R; Fromm M et al., Ophthalmic Research, 2005; 37: 179-187

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The presence and role of endothelin receptors in ciliary muscle (CM) and trabecular meshwork (TM) tissue and cells has been previously reported by a number of laboratories.^1-5 Functionally, however, ET's role in aqueous humor dynamics in the anterior chamber is still not clear. Choritz et al. (407) attempt to describe properties of the expressed ET receptors as to their contribution to contractile functions in CM and TM. The authors used bovine tissue and cells to describe the distribution of endothelin A and B receptors and to determine which of these receptors contributes to the contractile actions of ET-1. The authors present well controlled studies demonstrating that the ET_A receptor is primarily responsible for the contraction in both TM and CM, while the ET_B receptor appears to contribute little if any to this response. The authors have relied primarily on tissue contractions followed by calcium mobilization in isolated cells to assess these properties and Western blot analysis for receptor expression. This data supports previous observations on calcium signaling in these cells^1-3 and that endothelin contracts TM and CM.^5,6 This study has further characterized this response by identifying the ET_A receptor as the primary receptor responsible for contraction in bovine CM and TM. The authors were also unable to see an effect of the ET_B antagonist and attribute this lack of response to minimize ET_B's importance in endothelin actions in CM and TM. However, there were no studies utilizing ET_B agonists. Whether ET-1 lowers IOP or raises it is still not clear. It has been proposed that if ET-1's effects are predominate on TM, than a decrease in IOP may ensue. This has been shown in bovine anterior chamber eye perfusion experiments, where ET caused a decrease in aqueous humor outflow when only the TM was present with no CM.⁷ However, in case of the primate eye, perfusion experiments demonstrated an ET increase in outflow.⁸ Thus depending on the relative expression of receptors on the TM or CM, would an increase or decrease in IOP occur. This simplistic view does not account for any effects that may be attributed to ET_B receptors that have been shown to be linked to nitric oxide production and possible relaxation. Thus the interrelationships between receptor expression and tissue response may be critical. The present paper has highlighted this quite well in connecting receptor expression to functional responses in bovine tissue.

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