Retinal Biology Research Laboratory

Within: Discipline of Anatomy and Histology

Head of laboratory

On this page:

Overview

An overall unifying theme to our research has been the study of the retina as a model of the brain in order to further our understanding of the developmental biology of the glial cells and vasculature of the central nervous system. We have also studied the glial, vascular & immune response during retinopathy of prematurity (ROP), cerebral malaria, and inflammatory demyelinating disorders such as multiple sclerosis (MS) and physiological aging as a means of providing insight into the pathogenetic mechanism of early changes in age-related macular degeneration.

The laboratory has also made a major contribution to the understanding of the cellular mechanisms by which new vessels are formed in the retina and choroid during normal development, and in various disease processes. Since the retina is an extension of the brain, any insights we have gained have application and implication beyond the retina.

Other current projects in the laboratory aim to investigate the potential application of neural stem/precursor cells in animal models of MS and spinal cord injury. We aim to determine the best conditions required to generate pure populations of human spinal cord derived astrocytes, while further studies are underway to maximise cell differentiation along the oligodendrocytic and neuronal pathways.

Studies will ultimately be undertaken to maximize integration, migration and functional incorporation of transplanted cells in experimental models of disease.

Research achievements

Angiogenesis/Vascular Biology

1. Chan-Ling T, Halasz P and Stone J, “Development of retinal vasculature in the cat: processes and mechanisms” (1990) 9 Current Eye Research 459-478. (1.113) [82]
2. Chan-Ling T, Gock B and Stone J, “The effect of oxygen on vasoformative cell division: Evidence that 'Physiological hypoxia' is the stimulus for normal retinal vasculogenesis” (1995) 36 Investigative Ophthalmology and Visual Science 1201-1214. (Highest ranking journal for ophthalmology: IF: 4.148) [93] (e-publication at http://www.iovs.org/cgi/content/abstract/36/7/1201)
3. Stone J, Itin A, Alon T, Pe’er Y, Gnessin H, Chan-Ling T and Keshet E, “Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia” (1995) 15 Journal of Neuroscience 4738-4747. (8.306) [389] (e-publication at http://www.jneurosci.org/cgi/content/abstract/15/7/4738)
4. Contribution by personal invitation: Chan-Ling T, “Glial, neuronal and vascular cytogenesis in whole-mounted cat retina” (1997) 36(1) A special issue of Microscopy Research and Technique on retinal histology 1-16. (2.307) [58] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/55932/ABSTRACT)
5. Hughes S, Yang H, and Chan-Ling T, “Vascularisation of the human fetal retina: Roles of vasculogenesis and angiogenesis” (2000) 41(5) Investigative Ophthalmology and Visual Science 1217-1228. (4.148) [57] (e-publication at: http://www.iovs.org/cgi/reprint/41/5/1217?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=hughes&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=41&resourcetype=HWCIT)
6. Hughes S and Chan-Ling T, “Roles of endothelial cell migration and apoptosis in vascular remodelling during development of the central nervous system” (2000) 7 Microcirculation 317-333. (2.911) [20] (e-publication at http://taylorandfrancis.metapress.com/(iy2kt1ipdb2jhauo4gxeu445)/app/home/contribution.asp?referrer=parent&backto=issue,3,6;journal,43,55;linkingpublicationresults,1:111039,1)
7. Morcos Y, Hosie MJ, Bauer HC and Chan-Ling T, “Immunolocalisation of occludin and claudin-1 to tight junctions in intact CNS vessels of mammalian retina” (2001) 30(2) Journal of Neurocytology 107-123. (0.880) [23] (e-publication at http://www.springerlink.com/content/u4742p7175r65603/)
8. Chan-Ling T, McLeod S, Hughes S, Chu Y, Baxter L, Hasegawa T and Lutty G, “Astrocyte-endothelial cell relationships during human retinal vascular development” (2004) 45(6) Investigative Ophthalmology and Visual Science 2020-2032. (Highest ranking journal for ophthalmology: IF: 4.148) [27]. (e-publication at http://www.iovs.org/cgi/content/abstract/45/6/2020)
9. Hughes S and Chan-Ling T, “Characterisation of smooth muscle cells and pericyte differentiation in the rat retina in vivo” (2004) 45(8) Investigative Ophthalmology and Visual Science 2795-2806. (Highest ranking journal for ophthalmology: IF: 4.148) [36] (e-publication at http://www.iovs.org/cgi/content/abstract/45/8/2795)

Astrocyte Biology

1. Chan-Ling T and Stone J, “Factors determining the migration of astrocytes into the developing retina: Migration does not depend on intact axons or patent vessels” (1991) 303(3) Journal of Comparative Neurology 375-386. (3.672) [57] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/109691551/ABSTRACT)
2. Chan-Ling T and Stone J, “Factors determining the morphology and distribution of astrocytes in the cat retina: A ‘contact-spacing’ model of astrocyte interaction” (1991) 303(3) Journal of Comparative Neurology 387-399. (3.672) [43] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/109691552/ABSTRACT)
3. Holländer H, Makarov F, Dreher Z, van Driel D, Chan-Ling T, Stone J, “Structure of the macroglia of the retina: the sharing and division of labourbetween astrocytes and Muller cells” (1991) 313 Journal of Comparative Neurology 587-603. (3.672) [109] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/109692051/ABSTRACT)
4. Tout S, Dreher Z, Chan-Ling T and Stone J, “Contact-Spacing among astrocytes is independent of neighbouring structures In vivo and In vitro evidence” (1993) 332 Journal of Comparative Neurology 433-443. (3.672) [9] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/109692953/ABSTRACT)
5. Tout S, Chan-Ling T, Höllander H and Stone J, “The role of Müller cells in the formation of the blood-retinal barrier” (1993) 55 Neuroscience 291-301. (3.601) [73] (e-publication at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0F-485GF0K-6W&_coverDate=07%2F31%2F1993&_alid=502428315&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4861&_sort=d&view=c&_acct=C000008818&_version=1&_urlVersion=0&_userid=115085&md5=dfbce7a57beb9010ab9a642135bde470)
6. Morcos Y and Chan-Ling T, “Identification of oligodendrocyte precursors in the myelinated streak of the adult rabbit retina in vivo” (1997) 21(2) GLIA 163-182. (4.677) [9] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/53774/ABSTRACT)
7. Morcos Y, Shorey CDS and Chan-Ling T, “Contribution of O4+ oligodendrocyte precursors and astrocytes to the glial ensheathment of vessels in the rabbit myelinated streak” (1999) 27 GLIA 1-14. (4.677) [3] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/62003526/ABSTRACT)
8. Morcos Y and Chan-Ling T, “Concentration of astrocytic filaments at the retinal optic nerve junction is coincident with the absence of intra-retinal myelination: comparative and developmental evidence” (2000) 29 Journal of Neurocytology 665-678. (0.880) [13] (e-publication at http://www.springerlink.com/content/v7vhu6418850r850/)
9. Chu Y, Hughes S, and Chan-Ling T, “Differentiation and migration of astrocyte precursor cells and astrocytes in human fetal retina: relevance to optic nerve coloboma” (2001) 15(11) FASEB Journal 2013. (14.6) [30] (Please note the content of this 3-page summary is different to the full report that appeared on line.) (e-publication at http://www.fasebj.org/cgi/content/short/15/11/2013)
10. Kuo IY, Chan-Ling T, Wojcikiewicz RJ, and Hill CE, “Limited intravascular coupling in the rodent brainstem and retina supports a role for glia in regional blood flow”. (2008) 511 The Journal of Comparative Neurology 773-787. (Impact Factor: 3.915) (e-publication at: http://www3.interscience.wiley.com/cgi-bin/fulltext/121454717/PDFSTART)
11. Chan-Ling T, Baxter L, Weible II MW and Hughes S, “In vivo characterization of astrocyte precursor cells (APCs) and astrocytes in developing rat retinae; differentiation, proliferation and apoptosis”. (2009) 57 Glia 39-53. Impact Factor: 5.380)(Plus Cover Photo) (e-publication at: http://www3.interscience.wiley.com/cgi-bin/fulltext/120853974/PDFSTART)
12. Contribution by personal invitation: Chan-Ling T, “Glial, neuronal and vascular interactions in the mammalian retina” Progress in Retinal Research. Eds N. Osborne & G. Chader. Pergamon Press, Oxford. Vol 13, 357-389 1994. Highest ranking journal in ophthalmology. IF: 6.811) [39]

Neuropathology

1. Chan-Ling T, Neill AL and Hunt N, “Early microvascular changes in murine cerebral malaria detected in retinal wholemounts” (1992) 140 American Journal of Pathology 1121-1130. (6.946) [50]
2. Medana L, Chan-Ling T and Hunt NH, “Redistribution and degeneration of retinal astrocytes in experimental murine cerebral malaria: relationship to disruption of the blood-retinal barrier” (1996) 16 GLIA 51-64. (Plus Cover Photo) (4.677) [30] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/70755/ABSTRACT)
3. Ma N, Hunt N, Madigan M and Chan-Ling T, “Correlation between enhanced vascular permeability, up-regulation of cellular adhesion molecules and monocyte adhesion in the retina during fatal murine cerebral malaria” (1996) 149 American Joruanl of Pathology 1745-1762. (6.946) [36] (e-publication at http://ajp.amjpathol.org/cgi/content/abstract/149/5/1745)
4. Ma N. Madigan M, Chan-Ling T and Hunt N, “Compromised blood-nerve barrier, astrogliosis, and myelin disruption in optic nerves during fatal murine cerebral malaria” (1997) 19(2) GLIA 135-151. (4.677) [20] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/53693/ABSTRACT)
5. Medana L, Hunt N and Chan-Ling T, “Early activation of microglia in the pathogenesis of fatal murine cerebral malaria” (1997) 19(2) GLIA 91-103. (Plus cover photo) (4.677) [51] (e-publication at http://www3.interscience.wiley.com/cgi-bin/abstract/53689/ABSTRACT)
6. Hu P, Pollard J, Hunt N, Taylor J, and Chan-Ling T, “Microvascular and cellular responses in the optic nerve of rats with acute experimental allergic encephalomyelitis (EAE)” (1998) 8(3) Brain Pathology 475-486. (8.512) [21]
7. Hu P, Pollard J, Hunt N and Chan-Ling T, “Microvascular and cellular responses in the retina of rats with acute experimental allergic encephalomyelitis (EAE)” (1998) 8(3) Brain Pathology 487-498. (8.512) [11]
8. Medana I, Chan-Ling T and Hunt NH, “Reactive changes of retinal microglia during fatal murine cerebral malaria: effects of dexamethasone and experimental permeabilisation of the blood-brain barrier” (2000) 156(3) American Journal of Pathology 1055-1065. (6.946) [14] (e-publication at http://ajp.amjpathol.org/cgi/content/full/156/3/1055)
9. Hughes S, Yang H, and Chan-Ling T, “Vascularisation of the human fetal retina: Roles of vasculogenesis and angiogenesis” (2000) 41(5) Investigative Ophthalmology and Visual Science 1217-1228. (4.148) [57] (e-publication at: http://www.iovs.org/cgi/reprint/41/5/1217?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=hughes&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=41&resourcetype=HWCIT)
10. Potter SM, Chan-Ling T, Rosinova E, Ball HJ, Mitchell A, Hunt NH, “A role for Fas-Fas ligand interactions during the late-stage neuropathological processes of experimental cerebral malaria” (2006) 173(1-2) Journal of Neuroimmunology 96-107. (IF: 2.880)[12] (e-publication at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T03-4J2M46R-1&_coverDate=04%2F30%2F2006&_alid=502358152&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=4851&_sort=d&view=c&_acct=C000008818&_version=1&_urlVersion=0&_userid=115085&md5=b32b113438eb7a356f9a28dbb0e1ffe0)
11. Potter SM, Chan-Ling T, Ball HJ, Mitchell A, Maluish L, Mansour H, Hunt NH, “Perforin mediated apoptosis of cerebral Microvascular endothelial cells during experimental cerebral malaria” (2006) 36 International Journal of Parasitology 485-496. (IF: 3.337)[13] (e-publication at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7F-4J2VXXT-1&_coverDate=04%2F30%2F2006&_alid=502363882&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5057&_sort=d&view=c&_acct=C000008818&_version=1&_urlVersion=0&_userid=115085&md5=ffda534149f6e9fdcc7e539fcb8ba2f0)
12. Medana, IM, Chaudhri, G Chan-Ling, T & Hunt, NH, “The central nervous system in cerebral malaria: "innocent bystander" or active participant in the induction of pathology?” (2001) 79(2) Immunology and Cell Biology 101-120. (2.531) [21] (e-publication at http://www.blackwell-synergy.com/doi/abs/10.1046/j.1440-1711.2001.00995.x)
13. Hunt NH, Golenser J, Chan-Ling T, Parekh S, Rae C, Potter S, Medana IM, Miu J, Ball HJ, “Immunopathogenesis of cerebral malaria. (Review)” (2006) 36 International Journal of Parasitology 569-582. (Rank 9 out of 20 in the field of Parasitology IF: 3.092) [26] (e-publication at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T7F-4JHMH45-2&_coverDate=05%2F31%2F2006&_alid=502360141&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5057&_sort=d&view=c&_acct=C000008818&_version=1&_urlVersion=0&_userid=115085&md5=8263e564017a769227cebd12a5067e5e

Retinopathy of Prematurity

1. Chan-Ling T, Tout S, Holländer H and Stone J, “Vascular changes and their mechanisms in the feline model of Retinopathy of prematurity” (1992) 33 Investigative Ophthalmology and Visual Science 2128-2147. (Highest ranking journal for ophthalmology: IF: 4.148) [56] (e-publication at http://www.iovs.org/cgi/content/abstract/33/7/2128)
2. Chan-Ling T and Stone J, “Degeneration of astrocytes in feline retinopathy of prematurity causes failure of the blood-retinal barrier” (1992) 33 Investigative Ophthalmology and Visual Science 2148-2159. (Highest ranking journal for ophthalmology: IF: 4.148) [41] (e-publication at http://www.iovs.org/cgi/content/abstract/33/7/2148)
3. Chan-Ling T, Gock B and Stone J, “Supplemental oxygen therapy: Basis for non-invasive treatment of retinopathy of prematurity” (1995) 36 Investigative Ophthalmology and Visual Science 1215-1230. (Highest ranking journal for ophthalmology: IF: 4.148) [37] (e-publication at http://www.iovs.org/cgi/content/abstract/36/7/1215)
4. Stone J, Chan-Ling T, Pe'er J, Itin A, Gnessin H and Keshet E, “Roles of VEGF and astrocyte degeneration in the genesis of retinopathy of prematurity” (1996) 37 Investigative Ophthalmology and Visual Science 290-299. (Highest ranking journal for ophthalmology: IF: 4.148) [140] (e-publication at http://www.iovs.org/cgi/content/abstract/37/2/290)
5. Chan-Ling T and Hughes S, “Cell-cell interactions in the formation of the human retinal vasculature. Proceedings of the Third International Symposium on Retinopathy of Prematurity: An update on ROP from the lab to the nursery (November 2003, Anaheim, California)” (2006) Molecular Vision. (e-publication at http://www.molvis.org/molvis/v12/a63/) (2.777) [2]
6. Flynn JT & Chan-Ling T: “Retinopathy of prematurity: two distinct mechanisms that underlie zone 1 and zone 2 disease” (2006) 142(1) American Journal of Ophthalmology 46-59. (Ranked 9 out of 42 in the field of ophthalmology with IF: 2.3) [10] (e-publication at http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VK5-4K9JB47-6&_coverDate=07%2F31%2F2006&_alid=502357525&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6113&_sort=d&view=c&_acct=C000008818&_version=1&_urlVersion=0&_userid=115085&md5=c8126669335f463e83edab0e9376043c) [2]
7. Hughes S, Gardiner T, Baxter L, Chan-Ling T, “Smooth muscle cell and pericyte changes underlie pathogenesis of Plus Disease in Retinopathy of Prematurity” (2006) Nature Biotech Winter symposium on Angiogenesis, Miami Feb, 2006 Short report, web-based at www.med.miami.edu/mnbws/06Chan-Ling.pdf.
8. Hughes S, Gardiner T, Baxter L, Chan-Ling T, “Changes in pericytes and smooth muscle cells in the kitten model of Retinopathy of Prematurity (ROP): Implications for plus disease” (2007) 48 Investigative Ophthalmology and Visual Science 1368-1379. (IF: 4.418) [2] (e-publication at: http://www.iovs.org/cgi/reprint/48/3/1368?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=hughes+s&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT)
9. Invited review as the 1994 Australian Life Sciences Research awardee: Chan-Ling T, “From Kittens to Babies: The gift of sight” (1995) 7 Today's Life Science 26. (n/a) [n/a]

Stem Cell Biology

1. Chan-Ling T, Baxter L, Afzal A, Sengupta N, Caballero S, Rosinova E and Grant MB, “Hematopoietic stem cells provide repair functions after laser-induced Bruch’s membrane rupture model of choroidal neovascularisation” (2006) 168(3) American Journal of Pathology 1031-1044. (Highest ranking journal in pathology with impact factors of 8.51) [20] (e-publication at http://ajp.amjpathol.org/cgi/content/abstract/168/3/1031)
2. Chang KH, Chan-Ling T, McFarland EL, Afzal A, Pan H, Baxter LC, Shaw LC, Caballero S, Sengupta N, Calzi SL, Sullivan SM, and Grant MB, “IGF Binding Protein-3 Regulates Hematopoietic Stem and Endothelial Precursor Cell Differentiation, Migration and Retinal Development” (2007) 104 Proceedings of the National Academy of Sciences (PNAS) 10595 (Impact Factor: 15.053) [14]. (e-publication at: http://www.pnas.org/cgi/reprint/104/25/10595)
3. Weible MW II and Chan-Ling T, “Phenotypic characterization of neural stem cells from human fetal spinal cord: Synergistic effect of LIF and BMP4 to generate astrocytes” (2007) 55(11) Glia 1156-68 (Impact Factor: 5.500)(Plus Cover photo) [5] (e-publication at: http://www3.interscience.wiley.com/cgi-bin/fulltext/114284388/PDFSTART)
4. Kielczewski JL, McFarland EL, Jarajapu Y, Afzal A, Calzi S, Chang KH, Lydic T, Shaw LC, Busik J, Hughes J, Cardounel AJ, Wilson K, Lyons TJ, Cai J, Boulton ME, Mames RN, Gardiner T, Chan-Ling T, and Grant MB, “Insulin-like growth factor binding protein-3 (IGFBP-3) mediates vascular repair by enhancing nitric oxide generation”. (2009) Circulation Research Note: Kielczewski and McFarland and the two senior authors Chan-Ling and Grant contributed equally to this manuscript. Accepted J Circulation Research (IF: 12.755)
5. Howitt J, Putz U, Lackovic J, Doan A, Cheng H, Yang B, Chan-Ling T, Silke J, Kumar S and Tan SS. Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons. Accepted for publication PNAS 27th July 2009 Tracking #: 2009-04880R.

Aging

1. Hughes S, Gardiner T, Hu P, Baxter E, Rosinova E and Chan-Ling T, “Altered pericyte-endothelial relations in the aging rat retina: Implications for vessel stability” (2006) 27(12) Neurobiology of Aging 1838-1847. [11] (Highest impact factor under gerontology: 5.55) E article, available, Nov 2005. http://www.neurobiologyofaging.org/article/PIIS0197458005003490/abstract
2. Chan-Ling T, Hughes S, Baxter L, Rosinova E, McGregor I, Morcos Y, van Nieuwenhuyzen, PS and Hu P, “Inflammation and breakdown of the blood-retinal barrier during ‘physiological aging’ in the rat retina: a model for CNS aging” (2007) 14(1) Microcirculation 63. (IF: 2.955) [13] (e-publication at http://www.informaworld.com.ezproxy2.library.usyd.edu.au/smpp/content~content=a769178550~db=all~order=page)
3. Mansour H, Chamberlain CG, Weible II MW, Hughes S, Chu Y and Chan-Ling T, “Aging-related changes in astrocytes in the rat retina: Imbalance between cell proliferation and cell death reduces availability of astrocytes to neurons”. (2008) 7(4) Aging Cell 526-540. (Impact Factor: 5.854) (e-publication at: http://www3.interscience.wiley.com/cgi-bin/fulltext/119879262/PDFSTART)
4. Hunt GE, Nieuwenhuijzen PSV, Chan-Ling T and McGregor IS, “When an old rat smells a cat': a decline in defense-related, but not accessory olfactory, Fos expression in aged rats” 2009 Neurobiology of Aging 25th March 2009 In Press [IF: 5.999]
Book Chapters

1. Contribution by personal invitation: Chan-Ling T: The Blood Retinal Interface: Similarities and Contrasts with the Blood-Brain Interface. In: Dermietzel, R., Spray, D. C., Nedergaard, M. (Eds.): Blood-Brain Barriers - From Ontogeny to Artificial Interfaces. Wiley-VCH, Weinheim, p. 701-724. 2006.
2. Contribution by personal invitation: Chan-Ling T: Vasculogenesis and angiogenesis in formation of the retinal vasculature: cell-cell interactions and molecular cues. In Penn, J (Ed): Retinal and Choroidal Angiogenesis.Springer, The Netherlands, Chapter 6 p. 119-138, 2008.

Major collaborations
(Collaborator name, institution, plus optional brief description of project.)
Professor Maria Grant - Department of Pharmacology & Therapeutics, University of Florida
Collaborative studies to maximise the repair functions of hematopoietic stem cells in stemming vision loss. This work is funded by the Department of Educations, Science and Technology’s International Science Linkages Program.

Professor John Flynn – Harkness Eye Institute, Columbia University
Understanding Retinopathy of Prematurity: The Gift of Sight. Professor Chan-Ling currently holds the appointment of Adjunct Professor of Ophthalmic Science(Ophthalmology) at the Harkness Eye Institute of the Columbia University Medical Center ,New York

Dr. Tom Gardiner – Department of Ophthalmology & Visual Science, Queens University, Belfast
Collaborative studies utilising transmission electron microscopy to characterise changes in pericyte and smooth muscle cell ensheathment of retinal and choroidal blood vessels during normal development, in disease and in aging

Professor Jane Dahlstrom/Dr Mark Koina – Histopathology, Canberra Hospital, ACT
Collaborative work into cellular and molecular mechanisms of formation of the human choroidal and retinal vasculature.