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Notable Papers: The Polymodal Ion Channel Transient Receptor Potential Vanilloid 4 Modulates Calcium Flux, Spiking Rate, and Apoptosis of Mouse Retinal Ganglion Cells

Trpv4 is expressed in mouse ganglion cells

Glaucoma is a pernicious blinding disease affecting millions of people worldwide.  In some patients, the disease can be discovered early by measuring increases in intraocular pressure (IOP) – these patients are given hypotensive eye drops which can slow the progression of glaucoma. The real challenge has been, however, to determine the biological mechanisms through which increased pressure in the eye causes blindness. A group from the Moran Eye Center led by Dr. David Krizaj have recently published a paper in the Journal of Neuroscience which shows, for the first time, that stretching the membranes of retinal ganglion cells (which are the cells impacted in glaucoma), activates a specific ion channel which is permeable for the calcium ion. This increase in calcium influx through these TRPV4 channels made cells more excitable and, when sustained, killed them. This is the first time that a mechanism has been identified that couples mechanical stimulation to biological signals in cells affected by glaucoma.  Importantly, this discovery might clue us in why anti-IOP drugs help glaucoma patients as patients with particular TRPV4 variants may be innately susceptible to mechanical stimulation.


The authors of this paper were: Daniel A. Ryskamp, Paul Witkovsky, Peter Barabas, Wei Huang, Christopher Koehler, Nikolay P. Akimov, Suk Hee Lee, Shiwani Chauhan, Wei Xing, René C. Rentería, Wolfgang Liedtke and David Krizaj.



Categories: Notable papers, Retinal Disease, Vision Rescue.

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Continuing the Discussion

  1. […] Update 05/19/11: Work published in J. Neuroscience here.  Webvision entry in Notable Papers here. […]

  2. […] This notable paper by Roger C. Hardie and Kristian Franze looks at phototransduction in the fruit fly, Drosophila melanogaster.  Drosophila melanogaster has a long history in vision research of informing our understanding of the biochemical processes involved in phototransduction going back almost 40 years to this paper.  However, the Hardie and Franze paper looks at transient receptor potential (TRP) channels, which coincidently were also first found in Drosophila in a series of papers from Montel and Rubin, Hardie and Minke and Niemeyer et. al. and have proved themselves to be fairly ubiquitous and involved in wide areas of cell function from growth cones to cellular guidance and chemotaxis.  As expected, there are also many other areas where TRP channels are involved in the retina including store operated calcium channels and functions in ganglion cell calcium modulation, spiking rate and apoptosis. […]