Ocular Immunology Group
Professor Paul McMenamin
The Ocular Immunology group in The Department of Anatomy and Developmental Biology, led by Professor Paul McMenamin, is investigating a number of issues that relate to the normal development, normal aging and a number of eye diseases which may have an immune or inflammatory basis to their pathogenesis.
The World Health Organization estimates that over 45 M people are blind and 314 M people are visually impaired. The Ocular Immunology group has a number of active projects that are aimed at understanding common blinding diseases such as corneal infection, diabetic retinopathy and age-related macular degeneration. The research group sees itself as part of a larger global effort to understand these conditions – if we can help place one small piece in the large jigsaw puzzle of medical research that will help future treatment of these conditions then we will have succeeded. Prof McMenamin, who has 33 years experience in eye research believes in fostering a passion for eye research in his colleagues and hopes to help young scientists carve out their careers in this rewarding field either in his lab, in other Australian laboratories or overseas.
Current Research Interests
Eye Research
We have a number of active projects and have 2 current NH&MRC grants plus other smaller grants. The principle projects in the lab include:
· Role of monocyte-derived cells in corneal inflammation
· Role of microglia in diabetic retinopathy
· Potential relevance of macrophages in the subretinal space in mouse models of age-related retinal degeneration
· Transplantation of genetically engineered bone marrow cells to prevent autoimmune uveitis
· Membrane nanotubes as a novel means of cell-cell communication in the immune system
· Comparative ocular anatomy: lessons from nature about the structure and function of the eye
· Development of the eye and especially the role of macrophages in remodeling of the retina and lens
Other Research
In addition, Prof McMenamin has an interest in surgical and clinical anatomy. He is Director of ‘The Centre for Human Anatomy Education’ and supervises research projects in these areas plus topics in medical education relevant to anatomy education in medical curricula. He has pioneered the use of ‘Body Painting’ in the teaching of anatomy – a technique that has been taken up by several medical schools in Australia and overseas.
Techniques used in the Laboratory
There are many techniques used in the lab, including clinical monitoring, retinal and corneal imaging of the eye in live animals, live cell imaging, bone marrow transplantation, whole mount immunohistochemistry, histology and confocal microscopy.
Projects Available
Projects available for potential Honours/BiomedSci/PhD students
Are microglia in the retina activated in models of glaucoma?
To demonstrate that retinal microglia have a role in murine models of glaucoma Cx3cr1-gfp mice (in which nearly all of the monocyte-derived cells in the eye are GFP+ (fluorescent green)), allows us to examine the movement and behaviour of microglia in the eye. Colleagues at CERA (Centre for Eye Research Australia) have developed a model to mimic the changes in the eye secondary to raised pressure to investigate the pathological processes in glaucoma. We plan to induce raised pressure in the Cx3cr1-gfp mice and use clinical monitoring of disease (ophthalmoscopy and ERG) to monitor changes in retinal function. Post mortem retinal tissue will be analysed by confocal microscopy to examine activation markers in microglia and other retinal cells (eg astrocytes).
Are microglia in the retina activated in diabetes?
To demonstrate that retinal microglia have a role in diabetic retinopathy Diabetic mice (Akita) have been crossed with Cx3cr1-gfp mice to create a novel model ('Green Akitas' ) in which nearly all of the monocyte-derived cells in the eye are GFP+ (fluorescent green). This allows us to examine the movement and behaviour of microglia in the eye. We use many techniques including clinical monitoring of disease and tissue analysis by confocal microscopy to examine activation markers in these cells and other retinal cells (eg astrocytes and Muller cells).
The use of transgenic Zebrafish to investigate macrophage and neutrophil responses to ocular injury and in ocular development
Colleagues (Prof Graham Lieschke’s group) in the Australian Regenerative Medicine Institute (ARMI) have developed a number of genetically modified zebrafish in which immune cells express fluorescent markers. These have huge potential as model systems to investigate the basic biology of macrophages and neutrophils during development and repair. A number of potential projects using this model to investigate macrophages in eye development and the role of Toll like Receptors in corneal/ocular inflammation are possible and only await highly motivated candidates to help be pioneers in this emerging model system.
Research Group
Research Fellows
Dr Holly Chinnery
Dr Jelena Kezic
PhD students
Mr Yashar Razavi
Ms Xiangting Chen
Mr Kevin Su Men Chang
Dr Nina Vagaga (Lions Eye Institute)
Research Assistants
Ms Manpreet Sidhu
Dr Aaron Magno (Perth, LEI)
Collaborators
Professor Piroska Rakoczy (LEI)
Professor Mariapia Degli-Esposti (LEI)
Dr Erica Fletcher (University of Melbourne)
Professor John Forrester (Aberdeen University and Lions Eye Institute, UWA)
Professor Jonathan Crowston and Dr Ian Trounce (Centre for Eye Research Australia)
Grants
NHMRC Project Grant:
- Do resident immune cells cause retinal damage in diabetes? $428,000
- Role of Toll like receptors in corneal inflammation. $300,000
Publications
2011
T cell responses in experimental viral retinitis: Mechanisms, peculiarities and implications for gene therapy with viral vectors. Prog Retin Eye Res 2011; [Epub ahead of print]. Zinkernagel MS, McMenamin PG, Forrester JV, Degli-Esposti MA.
Accumulation of murine subretinal macrophages: effects of age, pigmentation and CX(3)CR1. Neurobiol Aging 2011; [Epub ahead of print]. Chinnery HR, McLenachan S, Humphries T, Kezic JM, Chen X, Ruitenberg MJ, McMenamin PG.
Intravitreal Triamcinolone Acetonide Induced Changes in the Anterior Segment in a Pig Model of Branch Retinal Vein Occlusion. Von Graefes Archives Ophthalmol 2011; 249(2): 215-22. Vijayasekaran S, McAllister IL, Morgan WH, Mendis KR, McMenamin PG, Yu Dao-Yi.
2010
The monocyte chemokine receptor CX3CR1 does not play a significant role in the pathogenesis of experimental autoimmune uveoretinitis. Invest Ophthalmol Vis Sci 2010; 51(10): 5121-7. Kezic JM and McMenamin PG.
Bone marrow chimeric mice reveal a role for CX3CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium. J Leuko Biol 2010; 88(4): 645-54. Vukovic J, Blomster LV, Chinnery HR, Weninger W, Jung S, McMenamin PG, Ruitenberg MJ.
Novel characterization of monocyte-derived cell populations in the meninges and choroid plexus and their rate of replenishment in bone marrow chimeric mice. Journal of Neuropathology and Experimental Neurology 2010; 69(9): 896-909. Chinnery, HR, Ruitenberg, MJ, McMenamin PG.
There is more than one way to vascularise a retina: a lesson in convergent evolution from our marsupial cousins. J Ophthal Photography 2010; (In Press). McMenamin PG.
Dendritic cell physiology and function in the eye. Immunological Reviews 2010; 234(1): 282-304. Forrester JV, Xu H, Kuffova L, Dick AD, McMenamin PG.
Teres minor innervation in the context of isolated muscle atrophy. Surg Radiol Anat 2010; 32(3): 243-9. Friend J, Frances S, McCulloch J, Ecker J, Breidahl W, McMenamin PG.
In vivo imaging of ocular MCMV infection. Invest Ophthalmol Vis Sci 2010; 51(1): 369-74. Zinkernagel MS, Petijean C, Fleming P, Chinnery HR, Constable IJ, McMenamin PG, Degli-Esposti MA.
Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration. Br J Ophthalmol 2010; 94(7): 918-25. Cherepanoff S, McMenamin PG, Gillies MC, Kettle E, Sarks SH.
The biceps brachii muscle and its distal insertion: observations of surgical and evolutionary relevance. Surg Radiol Anat 2010; 32(4): 371-5. Cucca YY, McLay SV, Okamoto T, Ecker J, McMenamin PG.
2009
Spectral domain OCT in Animal Research. Journal of Ophthalmic Photography 2009; 31: 94-96. Zinkernagel M, McMenamin PG, Constable I.
Stratification of antigen-presenting cells within the normal cornea. Ophthalmology and Eye Diseases 2009; 1 : 45-54. Knickelbein JE, Watkins SC, McMenamin PG, Hendricks RL.
Bone marrow chimeras and c-fms conditional ablation (Mafia) mice reveal an essential role for resident myeloid cells in LPS/TLR4 -induced corneal inflammation. JImmunol 2009; 182: 2738-44. Chinnery HR, Carlson EC, Sun Y, Lin M, Burnett SH, Perez VL, McMenamin PG, E Pearlman.
2008
CX3CL1 / fractalkine regulates branching and migration of monocyte-derived cells in the mouse olfactory epithelium. J Neuroimmunol 2008; 205: 80-5. Ruitenberg MJ, Vukovic J, Blomster L, Hall JE, Jung S, Filgueira L, McMenamin PG, Plant GW.
The Ida Mann Lecture: Planet Eye. Clin Experiment Ophthalmol 2008; 36: 592-599. McMenamin PG.
Turnover of bone marrow-derived cells in the normal mouse cornea. Immunology 2008; 125: 541-8. Chinnery HR, Humphries T, Clare A, Dixon AE, Howes K,Moran CB, Scott D, Zakrzewski M, Pearlman E, McMenamin PG.
Toll like receptors at the ocular surface. Ocul Surf 2008; 6: 108-116. Pearlman E, Johnson A, Adhikary G, Sun Y, Chinnery H, Fox T, Kester M, McMenamin PG.
Body painting as a teaching tool in medical education. Anatomical Sciences Education 2008; 1:139-144. McMenamin PG.
Differential turnover rates of monocyte-derived cells in varied ocular tissue microenvironments. J Leucocyte Biol 2008; 84: 721-9. Kezic J, McMenamin PG.
Cutting edge: Membrane nanotubes in vivo: A unique morphological feature of MHC class II+ macrophages and putative DCs in the mouse corneal stroma. J Immunol 2008; 180: 5779-5783. Chinnery HR, Pearlman E, McMenamin PG.
Retinal microglia and uveal tract dendritic cells and macrophages are not CX3CR1 dependant in their recruitment and distribution in the young mouse eye. Invest Ophthalmol Vis Sci 2008; 49:1599-1608. Kezic J, Xu H, Chinnery HR, Murphy CC, McMenamin PG.
Book: The Eye: Basic Sciences in Practice. 2008; Published by WB Saunders, London. 3rd Ed. Forrester JV, Dick A, McMenamin PG, Roberts F
Toll-like receptors at the ocular surface. Ocul Surf 2008; 6(3):108-16. Pearlman E, Johnson A, Adhikary G, Sun Y, Chinnery HR, Fox T, Kester M, McMenamin PG.
2007
The unique paired retinal vascular pattern in marsupials: structural, functional and evolutionary perspectives based on observations in a range of species. Brit J Ophthalmol 2007; 91:1399-1405. McMenamin PG.
The chemokine receptor, CX3CR1, mediates homing of MHC class II positive cells to the normal mouse corneal epithelium. Invest Ophthalmol Vis Sci 2007; 48:1568–1574. Chinnery HR, Ruitenberg MJ, Plant GW, Pearlman E, Jung S, McMenamin PG.
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