Glaucoma is the main cause of irreversible blindness in the world. In most common types of the disease, the optic nerve is damaged by an increase in intraocular pressure (IOP) which blocks fluid drainage through canals in the eye. There is currently no cure, however, the disease can be treated by lowering IOP. Unfortunately, all IOP-lowering drugs that in the market today target the secondary drainage pathway which mediates only 5-15% of fluid outflow. Therefore, the main goal in glaucoma research has been to identify targets in the primary outflow pathway mediated through the trabecular meshwork tissue. David Krizaj’s group at the Moran Eye Institute (University of Utah School of Medicine) has done just that.
In a paper just published in Scientific Reports, they identify TRPV4, a mechanosensitive ion channel, as the main trabecular target of increased IOP. This highly collaborative project combined genetic, molecular, whole animal approaches with bioengineered nanoscaffold models of glaucoma and drug discovery to show that activation of the channel mimics the trabecular changes in glaucoma whereas elimination of the TRPV4 gene or systemic exposure to TRPV4 inhibitors protected mice from the disease. In collaboration with Glenn Prestwich’s group in Medicinal Chemistry at the University of Utah, the team synthesized new eye drops which lowered IOP to levels seen in control mice. By targeting the primary outflow pathway, this study promises to bring new, effective cures that complement current glaucoma treatment. The primary authors of the study are Dr. Dan Ryskamp, Amber Frye and Dr. Tam Phuong.
There is a new publication out in the Journal of Neuroscience (cover story) from Moran Eye Center scientists, Store-Operated Calcium Entry In Müller Glia Is Controlled By Synergistic Activation Of TRPC And Orai Channels authored by Tünde Molnár, Oleg Yarishkin, Peter Barabas, Anthony Iuso, Bryan William Jones, Robert Marc, Tam Phuong, and David Krizaj.
This *very cool* paper in The Journal of Physiology (also featured in the F1000) by authors Tünde Molnar, Peter Barabas, Lutz Birnbaumer, Claudio Punzo, Vladimir Kefalov and David Krizaj examines mechanisms of cytosolic calcium levels in rod photoreceptor cells.
This poster was presented today at the Association for Research in Vision and Opthalmology (ARVO) meetings in Ft. Lauderdale, Florida by Judd M. Cahoon, Hironori Uehara, Ling Luo, Jacquelyn M. Simonis, Britt Dubil, Tadashi Miya, Paul R. Olson, Kortnie Walker, Bonnie Archer, Peter Barabas, David Krizaj, Gou Young Koh, Guangping Gao and Balamurali K. Ambati. Full size poster can be seen here.
This paper by Peter Barabas, Wei Huang, Hui Chen, Christopher L. Koehler, Gareth Howell, Simon W.M. John, Ning Tian, René C Rentería and David Križaj is an outcome of an attempt to follow glaucoma progression in the DBA/2J mouse model of a naturally occurring, late onset form of glaucoma. Ideally, a non-invasive technique should be used and in this case, they used a device to take advantage of the optomotor head turning reflex to assess progressive loss of vision. This reflex is very similar to the involuntary rotation of the eye in response to a rotating visual stimulus and it is present in all animals from fish to mammals (including humans). Interestingly, the DBA/2J strain was found to utterly lack this reflex.
ARVO 2011 has come and gone. Its taken me a couple of weeks to get through the post ARVO chaos and get caught up on my own work before posting some of the snapshots, but here they are. If you’d like to post your snapshots from ARVO here, send me an email (firstname.lastname@example.org) and we’ll arrange to add them to the list and credit you appropriately.