TRPM3 in the eye and in the nervous system – from new findings to novel mechanisms

Abstract

The calcium-permeable cation channel TRPM3 can be activated by heat and the endogenous steroid pregnenolone sulfate. TRPM3’s best understood function is its role as a peripheral noxious heat sensor in mice. However, the channel is expressed in various tissues and cell types including neurons as well as glial and epithelial cells. TRPM3 expression patterns differ between species and change during development. Furthermore, a plethora of TRPM3 variants that result from alternative splicing have been identified and the majority of these isoforms are yet to be characterized. Moreover, the mechanisms underlying regulation of TRPM3 are largely unexplored. In addition, a micro-RNA gene (miR-204) is located within the TRPM3 gene. This complexity makes it difficult to obtain a clear picture of TRPM3 characteristics. However, a clear picture is needed to unravel TRPM3’s full potential as experimental tool, diagnostic marker and therapeutic target. Therefore, the newest data related to TRPM3 have to be discussed and to be put in context as soon as possible to be up-to-date and to accelerate the translation from bench to bedside. The aim of this review is to highlight recent results and developments with particular focus on findings from studies involving ocular tissues and cells or peripheral neurons of rodents and humans.

Transcriptomic Changes Predict Metabolic Alterations in LC3 Associated Phagocytosis in Aged Mice

“…A variant in RDH5 has been shown to be associated with an increased skipping of exon 3, nonsense-mediated decay of the of aberrant transcript, and lower minor allele specific expression, thus providing a potential mechanistic link by which RDH5 allele contributes to AMD risk [ 64 ]. Interestingly, expression of both RDH5 and TRPM3 decreases under inflammatory conditions in vitro and has been suggested to contribute to RPE dysfunction in AMD [ 131 , 132 ]. TRPM3 codes for a calcium permeable cation channel activated by noxious heat, neurosteroid pregnenolone sulfate, or osmotic pressure [ 131 , 132 , 133 , 134 ].…”

“…Interestingly, expression of both RDH5 and TRPM3 decreases under inflammatory conditions in vitro and has been suggested to contribute to RPE dysfunction in AMD [ 131 , 132 ]. TRPM3 codes for a calcium permeable cation channel activated by noxious heat, neurosteroid pregnenolone sulfate, or osmotic pressure [ 131 , 132 , 133 , 134 ]. TRPM3 gene hosts miR-204 , a microRNA highly expressed in the RPE that plays an important role in gene regulation and retinal/RPE homeostasis [ 134 , 135 , 136 ].…”

A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain

“…Furthermore, these channels share a partly overlapping expression profile, especially in nociceptor neurons, and are involved in hypersensitivity and pathological pain signaling, offering challenging targets for analgesic drug development. 29 , 37 - 39 …”

Transcriptomic changes predict metabolic alterations in LC3 associated phagocytosis in aged mice

“…A variant in RDH5 has been shown to be associated with increased skipping of exon 3, nonsense-mediated decay of the of aberrant transcript, and lower minor allele specific expression, thus providing a potential mechanistic link by which RDH5 allele contributes to AMD risk [65]. Interestingly, expression of both RDH5 and TRPM3 decreases under inflammatory conditions in-vitro, and has been suggested to contribute to RPE dysfunction in AMD [132,133]. TRPM3, codes for a calcium permeable cation channel activated by noxious heat, neurosteroid pregnenolone sulfate, or osmotic pressure [132][133][134][135].…”

“…Interestingly, expression of both RDH5 and TRPM3 decreases under inflammatory conditions in-vitro, and has been suggested to contribute to RPE dysfunction in AMD [132,133]. TRPM3, codes for a calcium permeable cation channel activated by noxious heat, neurosteroid pregnenolone sulfate, or osmotic pressure [132][133][134][135]. TRPM3 gene hosts miR-204, a microRNA highly expressed in the RPE that plays an important role in gene regulation and retinal/RPE homeostasis [135][136][137].…”