WGA-Science-Award 2008 Ceremony

July 8, 2009, Boston

Winner of the WGA-Science-Award 2008 ‘The Present’ – for present impact: Abott Clark for his paper on ‘Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure’. Wang W-H, McNatt LG, Pang I-H, Millar JC, Hellberg PE, Hellberg MH, Steely HT, Rubin JS, Fingert JH, Sheffield VC, Stone EM, Clark AF. Journal of Clinical Investigation 2008; 118: 1056-1064

Laudatio by Paul Kaufman

The molecular etiology for glaucomatous pathophysiology in the trabecular meshwork (TM) is poorly understood. Inheritance clearly plays a role in glaucoma, but the identified glaucoma loci and several glaucoma genes account for only a small fraction of patients. Evaluation of differential gene and protein expression between normal and glaucomatous TM cells and tissues may help identify glaucoma pathogenic pathways. In order to determine whether such differences play an essential role in the pathogenic process or are merely associated secondarily with glaucoma, it would be important to know whether altered expression of the target gene causes glaucoma-like phenotypical changes in an appropriate model.

The authors used perfusion-cultured human ocular anterior segments and viral vector transgene expression in the mouse eye to confirm differentially expressed genes as meaningful glaucoma targets. They found that secreted frizzled-related protein-1 (sFRP-1), an antagonist of the Wnt signaling pathway, was differentially expressed in glaucomatous vs normal human TM cells. They further showed that human TM cells possess a functional Wnt signaling pathway, and that the addition of recombinant sFRP-1 to ex vivo perfusion-cultured human anterior segments decreased aqueous humor outflow facility, concomitant with reduced levels of β-catenin, the Wnt signaling mediator, in the TM. They also observed that overexpression of sFRP-1 in mouse eyes by intravitreal injection of an adenoviral vector encoding sFRP1 produced a titer-dependent 2-fold increase in IOP. Topical ocular administration of an inhibitor of glycogen synthase kinase-3 (GSK-3), a downstream suppressor of Wnt signaling, lowered IOP in sFRP-1–induced ocular hypertensive eyes. These data indicate that increased expression of sFRP1 in the TM appears to be responsible for elevated IOP in glaucoma, and that restoring Wnt signaling in the TM may be a novel glaucoma therapeutic strategy.

Laudatio by Keith Martin

For many years, our understanding of the dynamics and mechanisms of retinal ganglion cell (RGC) death in glaucoma has been limited by a dependence on post mortem histological studies. The inevitable consequence is that it has been impossible to understand fully how glaucoma affects individual RGC over time in the living retina. A further consequence has been that each animal only provides information about a single time point, requiring large groups to be used to study the time course of RGC loss. The work of Murata, Walsh, Leung and their co-workers highlights the potential of in vivo RGC imaging to radically change glaucoma research in the future. All three studies provide separate but complimentary evidence of the power of emerging imaging technologies. Leung and co-workers used a confocal scanning laser ophthalmoscope to track the loss of individual fluorescently labeled RGC after optic nerve crush in transgenic mice. Murata and colleagues achieved a similar result in following ischemia-reperfusion in the same mouse strain using a modified fundus camera. Walsh and Quigley, using a different strain of mice where only a small proportion of RGC are fluorescently labeled, were able to demonstrate the dendritic architecture of RGC in vivo in exquisite detail. The unusual decision of the judges to award The Promise Award to all three of these papers reflected the fact that 12 expert reviewers and the judging panel felt the contribution of all three to progress in the field was equal. Though not the first to image individual RGC, all the authors are to be congratulated for pushing the envelope of what is possible, and the possible implications for future glaucoma research are very clear.
The WGA-Science-Award has been made possible by an unrestricted educational grant from Pfizer Ophthalmics.

The following Awardees shared the WGA-Science-Award 2008 ‘The Promise’ – for potential future impact – on the same topic:

Hiroshi Murata, Makoto Aihara and Makoto Araie for their paper: ‘Imaging Mouse Retinal Ganglion Cells and Their Loss In Vivo by a Fundus Camera in the Normal and Ischemia-Reperfusion Model’. Hiroshi Murata, Makoto Aihara, Yi-Ning Chen, Takashi Ota, Jiro Numaga, and Makoto Araie, Investigative Ophthalmology and Visual Science 2008; 49: 5546-5552

Harry Quigley and Mark Walsch for their paper: ‘In vivo timelapse fluorescence imaging of individual retinal ganglion cells in mice’. Mark K. Walsh, Harry A. Quigley, Journal of Neuroscience Methods 2008; 169: 214-221

Harry Quigley (winner WGA-Science-Award ‘The Promise’)
and Remo Susanna (President WGA) (left to right)

Robert N. Weinreb and Christopher K.S. Leung for their paper: ’In vivo imaging of murine retinal ganglion cells’. Christopher K.S. Leung, James D. Lindsey, Jonathan G. Crowston, Won-Kyu Ju, Qwan Liu, Dirk-Uwe Bartsch, Robert N. Weinreb, Journal of Neuroscience Methods 2008; 168: 475-478

Christopher K.S. Leung (winner WGA-Science-Award ‘The Promise’), Remo Susanna (President WGA) and  Robert N. Weinreb (winner WGA-Science-Award ‘The Promise’) (left to right)