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Monash University > Medicine, Nursing and Health Sciences > Immunology > Research >

Diabetes and Vascular Biology Laboratory

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Laboratory Head

Prof. Jennifer Wilkinson-Berka
 
Phone: (03) 99030539
Email: Jennifer.wilkinson-berka@monash.edu

Department of Immunology
Monash University
Level 5, The Alfred Centre
99 Commercial Road
Melbourne  Victoria  3004
AUSTRALIA

Staff List

Research Fellow
Dr Antonia Miller
Dr Alex Agrotis
Mr Indrajeet Rana
Dr Roksana Armani

PhD Students
Devy Deliyanti
Pam Zhu Tong
Dean Talia (with Prof Fabienne Mackay)

Hons Student
TBA

Casual Staff
David Berka
Matthew Berka

Biography

My PhD was undertaken at The University of Melbourne, in the Department of Anatomy & Cell Biology and Dept. of Physiology, on the role of the renin-angiotensin-aldosterone system (RAAS) in kidney structure and function. Following completion of my PhD, I focused on diabetic complications and particularly the link between kidney and eye pathology, and was awarded the Sir Colin and Lady MacKenzie Fellowship in Comparative Anatomy. Over the next few years I developed animal models of diabetic retinopathy and retinopathy of prematurity, and in 1999 established the Diabetes and Retinopathy Laboratory in the Department of Physiology, Melbourne University. In 2004, I was promoted to Associate Professor, and in 2006 was awarded a NHMRC Senior Research Fellowship B. In late 2006, I joined the Department of Immunology, AMREP, Monash University, with the view to expanding my research into the field of immunology and consolidate my interests in diabetic complications with researchers in the Baker IDI Heart and Diabetes Institute. In 2010, I was promoted to Professor by Monash University. In 2011, my NHMRC Fellowship was renewed and I was appointed Deputy Head (Research) of the Department of Immunology.

Research interests

In our community and worldwide, the major causes of vision loss are attributable to three diseases. Retinopathy of prematurity (ROP) is the commonest cause of vision loss in infants. Retinopathy is the most feared complication of diabetes, and develops in almost all patients with Type 1 diabetes. Age-related macular degeneration (AMD) is the main reason for vision loss in people over 65 years. The prevalence of these diseases has dramatically increased in recent years and for diabetic retinopathy is expected to reach epidemic proportions due to a global rise in obesity and a range of environmental influences. Today, the underlying factors that contribute to these diseases remain elusive, and without further scientific advancements we are faced with a considerable health and economic burden. Our laboratory’s research is focused on understanding the contribution of vasoactive factors to these diseases. We made the original discovery of the cellular location of the RAAS in the eye, and showed that its blockade prevented the development of vascular disease in retinopathy of prematurity. These and subsequent studies in diabetic retinopathy became the basis for the largest clinical trial to date, which tested the effect of angiotensin type 1 receptor blockade in over 5000 diabetic patients – the DIRECT programme 2008. This trial together with recent studies, suggest that RAAS blockade may find a place as a new and non-invasive treatment for diabetic retinopathy. Our goal is to now move forward to understand in more detail how other components of the RAAS are involved in retinal diseases. The RAAS is complex, and it is likely that inhibiting or augmenting other key components will provide even further retinal protection. We have a multi-disciplinary approach to our research, which involves using and developing pre-clinical models of retinal disease (both in vivo and in vitro), morphological analysis of disease progression, molecular and protein expression assays, biochemical and analytical chemistry and functional testing. We are also excited about new projects designed to understand the involvement of the immune system and epigenetics to disease progression.

Key Collaborators

Our research success would not be possible without the valuable input from our collaborators in Australia and around the world.

Prof Mark Cooper, Prof Merlin Thomas, Dr Chris Tikellis, Associate Prof Terri Allen and Prof Karin Jandeleit-Dahm, Baker IDI Heart and Diabetes Institute, Melbourne.
Prof Fabienne Mackay, Department of Immunology, Monash University, Melbourne
Associate Prof Erica Fletcher, Department of Anatomy and Cell Biology, The University of Melbourne
Prof Duncan Campbell, St Vincent’s Institute of Medical Research, Melbourne.
Prof Genevieve Nguyen, INSERM and College de France, Paris, France
Prof Janos Peti-Peterdi, University of Southern California, Los Angeles, USA
Prof Rhian Touyz, University of Ottawa, Ottawa, Canada

Projects

We have available a variety of Honours and PhD projects.

  • The role of the renin-angiotensin system in the normal and adaptive immune system in retinopathy.
  • Understanding the stimuli for renin release in diabetic retinopathy: a role for succinate and its receptor, GPR91.
  • The newly discovered (pro)renin receptor: how does it contribute to diabetic retinopathy and retinopathy or prematurity?
  • Aldosterone and the mineralocorticoid receptor: roles in retinal inflammation and disease
  • The contribution of microglia to retinopathy: mechanisms involving reactive oxygen species derived from NADPH oxidase.
  • Advanced glycation end-products and diabetic retinopathy
  • Epigenetics and diabetic retinopathy
  • Angiotensin converting enzyme 2 (ACE2): a protective role in diabetic retinopathy and retinopathy of prematurity?

Publications

Wilkinson-Berka  JL, Tan G, Binger K, Sutton L, McMaster  K, Perera G, Campbell DJ and Miller AG, “Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen induced retinopathy, Diabetologia, 2011, 54, 2724-35.

Wilkinson-Berka JL, Miller AG, Binger KJ, “Prorenin and the (pro)renin receptor: recent advances and implications for retinal development and disease”, Curr. Opin. Nephrol. Hypertens., 2011, 20(1), 69-76.

Wilkinson-Berka JL, Allen TJ, Miller AG, Prorenin and the (pro)renin receptor in retinal pathology, Clin. Exp. Hypertens. 2010.

Wilkinson-Berka JL, Miller AG, Fletcher EL, Prorenin and the (pro)renin receptor: Do they have a pathogenic role in the retina? Front. Biosci. (Elite Ed), 2010, 2, 1054-64.

VESSEY KA, WILKINSON-BERKA JL, FLETCHER EL. Characterization of retinal function and glial cell response in a mouse model of oxygen-induced retinopathy. J Comp Neurol 519:506-527, 2011

MILLER AG, TAN G, BINGER KJ, PICKERING RJ, THOMAS MC, NAGARAJ RH, COOPER ME, WILKINSON-BERKA JL. Candesartan attenuates diabetic retinal vascular pathology by restoring glyoxalase-I function. Diabetes 59:3208-3215, 2010

WILKINSON-BERKA JL, HEINE R, TAN G, COOPER ME, HATZOPOULOS KM, FLETCHER EL, BINGER KJ, CAMPBELL DJ, MILLER AG. RILLKKMPSV influences the vasculature, neurons and glia, and (pro)renin receptor expression in the retina. Hypertension 55:1454-1460, 2010 FLETCHER EL, PHIPPS JA, WARD MM, VESSEY KA, WILKINSON-BERKA JL. The renin-angiotensin system in retinal health and disease: Its influence on neurons, glia and the vasculature. Prog Retin Eye Res 29:284-311, 2010

WILKINSON-BERKA JL, TAN G, JAWORSKI K, MILLER A. Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on vascular pathology. Circulation Research 104:124-133, 2009

DOWNIE LE, VESSEY K, MILLLER A, WARD MM, PIANTA MJ, VINGRYS AJ, WILKINSON-BERKA JL, FLETCHER EL. Neuronal and glial cell expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in rat retina. Neuroscience 161:195-213, 2009

WILKINSON-BERKA JL, CAMPBELL DJ. (Pro)renin receptor in Diabetic Retinopathy. Diabetes 58:1485-1487, 2009

DOWNIE LE, PIANTA MJ, VINGRYS AJ, WILKINSON-BERKA JL, FLETCHER EL. AT1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen-induced retinopathy. Glia 56:1076-1090, 2008

MORAVSKI CJ, SKINNER SL, STUBBS AJ, SARLOS S, KELLY DJ, COOPER ME, GILBERT RE, WILKINSON-BERKA JL. The renin-angiotensin system influences ocular endothelial cell proliferation in diabetes: transgenic and interventional studies. Am J Pathol 162:151-160, 2003

MORAVSKI CJ, KELLY DJ, COOPE ME, GILBERT RE, BERTRAM JF, SHAHINFAR S, SKINNER SL, WILKINSON-BERKA JL. Retinal neovascularization is prevented by blockade of the renin-angiotensin system. Hypertension 36:1099-1104, 2000 WILKINSON-BERKA JL, BABIC S, DE GOOYER TE, STITT AW, JAWORSKI K, ONG GT, KELLY DJ, GILBERT R. Inhibition of platelet derived growth factor promotes pericyte loss and angiogenesis in ischaemic retinopathy. Am J Pathol 164:1263-73, 2004

KELLY DJ, WILKINSON-BERKA JL, ALLEN TJ, COOPER ME, SKINNER SL. A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2)27 rat (TGR). Kidney Int 54:343-352

GILBERT RE, VRANES D, BERKA JL, KELLY DJ, COX A, WU LL, STACKER SA, COOPER ME. Vascular endothelial growth factor and its receptors in control and diabetic rat eyes. Lab Invest 78:1017-1027, 1998

BERKA JL, STUBBS AJ, WANG DZ, DINICOLANTONIO R, ALCORN D, CAMPBELL DJ, SKINNER SL. Renin-containing Müller cells of the retina display endocrine features. Invest Ophthalmol Vis Sci 36:1450-1458, 1995

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