Glaucoma Research Laboratory
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Head Glaucoma Research Laboratory
Jonathan Crowston+61 3 9929 8429
Research Overview
Our recent work conducted in rodents and humans has explored the utility of Retinal Ganglion Cell-derived components of the electroretinogram (ERG) for assessing retinal ganglion cell (RGC) function. (The ERG measures the electrical activity of the retina in response to light stimulation.) Two subcomponents of the full-field ERG - the photopic negative response and the positive scotopic threshold response - are largely derived from RGCs and provide a measure of the cell's function which in turn reflects cell health. We have made substantial progress in improving measurement reproducibility and shown short-term improvement in RGC function in glaucoma patients 1-month after initiation of treatment and in rodents following an acute IOP injury. Subsequent patch-clamping studies have provided further insights into the structural and functional changes in individual RGCs that accompany loss and recovery of function as determined by the ERG. We hypothesise that short term changes in RGC function (PhNR, and pSTR) will predict longer-term progression rates as determined by standard perimetry and optic nerve and retinal nerve fibre layer imaging (the current standards that require at least 2-years to detect change).
We are currently conducting a longitudinal cohort study to determine whether short-term ERG changes accurately predict rates of glaucoma progression in the longer term. Second, we will use hyperspectral imaging to analyse changes in the spectral characteristics of reflected light from the RGC layer that are associated with loss or gain of the ERG signals and thus inform on the state of RGC health. The overall goal is to define structural and functional markers of RGC health that accurately distinguish fast and slow progressors in the longer term.
Staff
Dr Vicki Chrysostomou - Glaucoma Research Fellow
Dr Xavier Hadoux - Glaucoma Research Fellow
Dr Zhichao Wu - Glaucoma Research Fellow
Flora Hui - Glaucoma Research Fellow
Dr Marc Sarossy - Senior Research Fellow
Jess Tang - MPhil Student
Collaborators
Prof Franz Grus - Department of Ophthalmology, University of Mainz, Germany
Dr Nick Marsh - ArmstrongJohn Hopkins University, USA
Dr Gregory Steinberg - McMaster University, Ontario, Canada
Prof Robert Casson - South Australian Institute of Ophthalmology Adelaide
Prof Steve Petrou -Florey Department of Neuroscience and Mental Health
Assoc Prof Ian Trounce - Ophthalmology, University of Melbourne
Dr Peter van Wijngaarden- Ophthalmology, University of Melbourne
Funding
National Health & Medical Research Council
Ophthalmic Research Institute of Australia
BrightFocus Foundation
Connie and Craig Kimberley
The Miller Foundation Ltd
Research Outcomes
Crowston JG, Y. Kong XY, Trounce IA, T. Dang TM, E. Fahy ET, Bui BV, Morrison JC, Chrysostomou V (2015). An Acute Intraocular Pressure Challenge to Assess Retinal Ganglion Cell Injury and Recovery in the Mouse. Exp Eye Res (2015).
Razali N, Agarwal R, Agarwal P, Kumar PS, Tripathy M, Vasudevan MS, Crowston JG, Ismail NM (2015). Role of adenosine receptors in resveratrol-induced intraocular pressure lowering in rats with steroid-induced ocular hypertension. Clin Experiment Ophthalmol, 43 (2015), 54-66.
Goldberg I, Graham SL, Crowston JG, d'Mellow G, Australian, New Zealand Glaucoma Interest Group (2015). Clinical audit examining the impact of benzalkonium chloride-free anti-glaucoma medications on patients with symptoms of ocular surface disease. Clin Experiment Ophthalmol 43:214-220.
Perera C, Chakrabarti R, Islam FM, Crowston J (2015). The Eye Phone Study: reliability and accuracy of assessing Snellen visual acuity using smartphone technology. Eye (Lond), 29:888-894
Ross C, Pandav SS, Li YQ, Nguyen DQ, Beirne S, Wallace GG, Shaarawy T, Crowston JG, Coote M (2015). Determination of bleb capsule porosity with an experimental glaucoma drainage device and measurement system. JAMA Ophthalmol 133:549-554.
Skalicky SE, Martin KR, Fenwick E, Crowston JG, Goldberg I, McCluskey P (2015). Cataract and quality of life in patients with glaucoma. Clin Experiment Ophthalmol 43:335-341.
Lamoureux EL, McIntosh R, Constantinou M, Fenwick EK, Xie J, Casson R, Finkelstein E, Goldberg I, Healey P, Thomas R, Ang GS, Pesudovs K, Crowston J (2015). Comparing the effectiveness of selective laser trabeculoplasty with topical medication as initial treatment (the Glaucoma Initial Treatment Study): study protocol for a randomised controlled trial. Trials 16:406.
Noh SM, Abdul Kadir SH, Crowston JG, Subrayan V, Vasudevan S (2015). Effects of ranibizumab on TGF-beta1 and TGF-beta2 production by human Tenon's fibroblasts: An in vitro study. Mol Vis 21:1191-1200.
Skalicky SE, Fenwick E, Martin KR, Crowston J, Goldberg I, McCluskey P (2015). Impact of age-related macular degeneration in patients with glaucoma: understanding the patients' perspective. Clin Experiment Ophthalmol. 2015, Oct 20. doi: 10.1111/ceo.12672.
Van Bergen NJ, Crowston JG, Craig JE, Burdon KP, Kearns LS, Sharma S, Hewitt AW, Mackey DA, Trounce IA (2015). Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy. PLoS One 10:e0140919.
Crowston JG, van Wijngaarden P (2016). Glaucoma neurorecovery - a sugar-coated road to retinal ganglion cell recovery. Clin Experiment Ophthalmol 44:6-7.
Fahy ET, Chrysostomou V, Crowston JG (2015). Impaired Axonal Transport and Glaucoma. Current eye research 1-11
Fahy ET, Chrysostomou V, Crowston JG (2016). Mini review: Impaired Axonal Transport and Glaucoma. Current eye research 41:273-283.
Fahy ET, Chrysostomou V, Abbott CJ, van Wijngaarden P, Crowston JG (2016). Axonal transport along retinal ganglion cells is grossly intact during reduced function post-injury. Exp Eye Res 146:289-292.
Kerr NM, Kumar HK, Crowston JG, Walland MJ (2016). Glaucoma laser and surgical procedure rates in Australia. Br J Ophthalmol.
Wu Z, Hadoux X, Fan Gaskin JC, Sarossy MG, Crowston JG (2016). Measuring the Photopic Negative Response: Viability of Skin Electrodes and Variability Across Disease Severities in Glaucoma. Transl Vis Sci Technol 5:13.
Research Publications
Aung T, Ozaki M, Mizoguchi T et al. A common variant mapping to CACNA1A is associated with susceptibility to exfoliation syndrome Nature Genetics. 2015; 47(4):387-92. Describes a new genetic locus for pseudoexfoliation glaucoma.
Chrysostomou V, Kezic JM, Trounce IA, Crowston JG. Forced exercise protects the aged optic nerve against intraocular pressure injury. Neurobiol Aging. 2014; 35(7):1722-5. First evidence for exercise improving retinal recovery after injury and reversing the negative impact of ageing.
Lee S, Sheck L, Crowston JG, Van Bergen NJ, O'Neill EC, O'Hare F, Kong YX, Chrysostomou V, Vincent AL, Trounce IA. Impaired complex-I-linked respiration and ATP synthesis in primary open-angle glaucoma patient lymphoblasts. Invest Ophthalmol Vis Sci. 2012; 53(4):2431-7. The first description of an OXPHOS complex-1 defect in a cohort of open angle glaucoma patients.
Kong YX, Van Bergen N, Trounce IA, Bui BV, Chrysostomou V, Waugh H, Vingrys A, Crowston JG. Increase in mitochondrial DNA mutations impairs retinal function and renders the retina vulnerable to injury. Aging Cell. 2011; 10(4):572-83. First manuscript to demonstrate that mitochondrial impairment impaired recovery following injury induced by eye pressure.
Kong YX, van Bergen N, Bui BV, Chrysostomou V, Vingrys AJ, Trounce IA, Crowston JG. Impact of aging and diet restriction on retinal function during and after acute intraocular pressure injury. Neurobiol Aging. 2012; 33(6):1126.e15-25. First manuscript to demonstrate that age-related vulnerability to eye pressure injury can be effectively reversed by diet restriction.