VISION DEVELOPMENT LABORATORY

Ann E. Sefton

The research of the Laboratory is principally directed towards understanding the development and regeneration of the visual system in mammals. In collaboration with Paul Martin's group, the Laboratory is also studying the structure and function of the visual pathways in adult primates.

RESEARCH in 1993

Trophic support of developing retinal ganglion cells

A chondroitin sulphate proteoglycan molecule, recently purified from the brains of developing rats, in the Neurobiology Laboratory of Max Bennett, has been demonstrated to be a retinal ganglion cell neurotrophic factor in vitro. The effect of the factor was studied on the growth and development of retinal ganglion cells in vivo. The eyes of neonatal rats have been injected with the putative trophic factor and determination of the number of axons in the optic nerve demonstrated a greater survival in the treated animals. High concentrations appeared to be somewhat toxic. In a second series of experiments, a molecule, which contains the HNK1 epitope also present in the collicular proteogycan, has been extracted from the thalamus of neonatal rats. It appeared to support well the survival of retinal ganglion cells in vitro. Further experiments are continuing to determine its nature and effects and to characterize its nature.

Trophic support for damaged optic axons

Retinal transplants: In a collaboration begun with Ray Lund and Mark Hankin, the technique of transplantation of embryonic retinal tissue was used to study the early outgrowth of the projecting first axons. It was found that axons extended, from retinal transplants placed in the cortex, only when they were able to follow an existing pathway, enter a region of damage. None survived beyond about one week in the absence of a normal target region.

Damage to adult neurones

It is known that neurones from the adult central nervous system rarely survive a traumatic lesion. Experiments were therefore conducted to test whether the chondroitin sulfate proteoglycan purified in the Laboratory of Max Bennett could be as effective in the rescue of adult, axotomized retinal ganglion cells as it was in the rescue of neonatal retinal ganglion cells. This proteoglycan was found to prevent the degeneration of about 63% of adult retinal ganglion cells if injected intraocularly for two weeks after the lesion. Such a significant result indicated that injured adult central neurones, unlike their healthy counterparts, may depend on trophic factors derived from their targets in order to survive traumatic lesions.

New classification for rat retinal ganglion cells

The retinal ganglion cells of most mammals have been described and classified into functional groups, each with a characteristic morphology. In the rat, however, this classification relied upon morphological techniques such as tracing of retinal ganglion cells with horseradish peroxidase or staining of Golgi which rarely filled the whole dendritic tree. The Laboratory has used a combination of two labelling techniques, namely tracing with DiI and intracellular injections with neurobiotin, to completely fill the dendritic trees and somata of retinal ganglion cells in the adult albino rat. These superior techniques allowed ganglion cells to be categorized according to established criteria. Many types of ganglion cells, that had not been previously described, were, however, found. A new classification scheme was therefore created for rat retinal ganglion cells. The determination of the types of ganglion cells in this animal will enable the Laboratory to gather more precise information as to the visual capabilities of the rat, phylogenetic information regarding ganglion cell classes and reactions of different types of ganglion cells to trauma or degenerative disorders.

Thalamic reticular nucleus and the lateral-posterior pulvinar complex

Further studies were carried out, in collaboration with Tom Fitzgibbon, on the interrelationships between the thalamic reticular nucleus and the lateral-posterior pulvinar complex in the cat. The presence of a precise topographic relationship was established.

RESEARCH PLANNED for 1994

During 1994, collaborative work with Paul Martin will continue in studies of the visual system of the marmoset. In addition, a new collaboration with Max Bennett's Laboratory will commence, with studies of cells of the developing rat lateral geniculate nucleus. The effects of nitric oxide on synaptic interactions will be investigated using patch clamp techniques. The regenerative effects in vivo of the retinal ganglion cell neurotrophic factor will be investigated further in adult animals after lesions to the optic nerve, and a parallel study on the effects of lesions on the classes of retinal gangion cells in the rat will be concluded. The potential trophic factor extracted from the thalamus will be further investigated and studies will continue on the effect of potential growth factors on retinal ganglion cells by studying calcium activation.

PERSONNEL in 1992 and 1993

Dr Ann E. Sefton	Professor (in-charge) 		University	1974-
Dr Ann Goodchild 	Research Assistant, Grade 2	NHMRC		1992-
			(with P.R. Martin)
Gavin J. Dixon		PhD student 			APRA		1987-93
Paul Armson		PhD student (1/4)				1991-
Krystel Huxlin		PhD student		  	APRA		1990-
Loreto Tevah		former BSc(Hons) student			1992-3
Krishna Ghosh		BSc(Hons) student				1993
			(with P.R. Martin)
Affiliate
Dr Tom Fitzgibbon	Dept of Clinical Ophthalmology (1/5)		 1990-
Current effective full-time personnel = 3.25

COLLABORATIONS

Development of retino-collicular topography: Dr Bogdan Dreher, Dept of Anatomy (1992-present).

Early axonal outgrowth - the effect of retina ganglion cell neurotrophic factor: Prof. Ray D. Lund (from 1992 at Cambridge Univ.) and Dr M.H. Hankin (from 1992 at Medical College of Ohio, Toledo) (1990-1993).

Studies on the visual pathway of the cat: Dr Tom Fitzgibbon, Dept of Clinical Ophthalmology (1991-present).

Studies on the visual system of the marmoset monkey: Dr Paul R. Martin (1993-present).

FACILITIES

The laboratory work area comprises rooms 425, 426, 427 and 431 of the Anderson Stuart building. Dr Sefton's office is room 429 and other personnel occupy room 430. Equipment includes: high quality light (transmission and fluorescent) and dissecting microscopes, Imagellan image analysis systems, photomicrography, facilities for immunohistochemistry, histochemistry and various neuro-anatomical tracing techniques, laminar flow cabinet, incubator, surgical, anaesthetic and some electrophysiological equipment, Macintosh and Apple II personal computers and accessories.

FUNDING in 1993 and 1994

NHMRC	The visual system in dichromatic and	Martin PR	1993	 *$73,862
	trichromatic marmoset monkeys		Sefton AE	1994	**$61,334
	(*Lab's share = $22,147;				1995
	**Lab's share = $12,267)			

Total for 1993: $22,147

Total for 1994: $12,267

SCHOLARSHIPS in 1993 and 1994

Australian Postgraduate Research Award	Dixon G		1987-93
Australian Postgraduate research award	Huxlin K	1990-
TEACHING in 1993

Medicine 3

Course Supervisor for Neuroscience course (interdepartmental).

Lectures: 23.

Practical classes: 5, each of 2 h, repeated once (total h = 20).

Demonstrations: 3, each of 2 h, some repeated (total h = 12).

Tutorials: 4 revision, each of 2 h (total h = 10).

Science 3, BMedSc 3

Lectures: 10, on central nervous system, plasticity and development.

Practical classes: 3, each of 3 h, repeated once.

Total distribution (hours of formal teaching)

				Med3	Sci3	Total	

Lectures			23	10	45	
Practical classes (no.)		20(10)	18(6)	38	
Demonstrations			12	-	12	
Tutorials			4	-	8
Total formal contact teaching time = 103 h*.

Note that Ann Sefton was on a Special Studies Program as a Visiting Professor at Harvard Medical School during 2nd semester, 1993. During that time, she taught a number of problem-based tutorials to second year medical students at Harvard in a course entitled Human Nervous System and Behaviour and was involved in a first year program on Metabolism and Function.

Assessment

Setting and marking exams in all courses taught, together with essays in the Sci3/BMedSc3 course and the Med3 course Neuroscience; was also involved in assessment at Harvard in Human Nervous System and Behaviour.

Student consultations

As Associate Dean, numerous visits from medical students of all years were entertained throughout the year, as well as from those seeking admission to Medicine. Assistance was offered to students in all courses taught.

Curriculum design

New medical degree:

Chair of the Planning Committee for the Graduate Medical Program; Member of all Working Parties ex officio.

Responsible for liaison with the Consortium of Graduate Medical Schools at Univ. of Queensland and Flinders Univ.

Sydney representative on the Policy Committee for the Graduate Australian Medical Schools Admission Test.

Course administration

New BMedSc degree: Member of the committee for the core course Human Life Sciences

Reports relating to teaching

Admissions to the Faculty of Medicine (profile of 1993 entrants).

Admission policy (interpreted in student brochures and for student magazines in articles concerning careers advice).

Prepared documents associated with planning for the Graduate Medical Program, including papers circulated to Faculty, articles in the graduate newsletter, Radius. In addition, articles were written for the Faculty’s newsletter Medical Scripts and shorter pieces for each issue of an ephemeral newsletter on planning. Advice to schools and potential applicants was also prepared.

OTHER ACTIVITIES in 1993

Award

Award for Achievement in Education, Australasian and New Zealand Association for Medical Education.

Refereeing

Manuscript: for Medical Journal of Australia (1). Grant (and fellowship) applications: for National Health and Medical Research Council (6), Australian Research Council (2) Department of Industry, Technology and Commerce (1), OPSM (1), Committee for the Advancement of University Teaching (1).

University committees

Member, Advisory Committee, Learning Assistance Centre.

Faculty of Medicine representative on the Centre for Gay and Lesbian Studies.

Academic Board

Active member.
Member, Admissions Committee.
Member, Broadway Review Committee.
Member, Committee on Undergraduate Studies
Chair, Examinations, Assessments and related matters.
Member, Committee on Gender Balance on the Board and its committees.
Represented Chair on appointments/promotions committees.
Faculty of Medicine

Associate Dean (Curriculum) 
Member, Dept of Clinical Ophthalmology.
Member, Postgraduate Degree Planning Committee (Chair).
Chair, Boards of Examiners for Years 1-3, BSc(Med)(Hons) and Review Committees.
Chair, Admissions Committee.
Co-chair, Executive Curriculum Committee.
Chair, Appointment Committees, Level A (Chair)
Member, other appointment committees.
Member, Save Sight Foundation.
Member (ex officio), Dean's Planning and Advisory Committee.
Member (ex officio), Faculty Management and Advisory Committee.
Member, Australian Medical Council Accreditation Steering Committee.
Member, Course Evaluation Committee.
Member, Committee to consider Gender Balance in the Faculty.
Member, Committee on the teaching of Ethics and Law.
Member, Committee for Medical Communication.
Member, Interdepartmental Committee for History & Philosophy of Medicine course.
Member, Year Committees: Years 1-2, Year 3.
Member (ex officio), Clinical Diagnosis Committee, Year 3.
Member, Standing Committee. 
Member (ex officio), Standing Committee on Courses of Study.
Member, Steering Committee for Strategic Plan.
Member, Anderson Stuart Restoration Committee.
Member, Centenary Medical Fellowships for Technicians Committee
Member, Medical Graduates Publication Committee.
Conference organizing committee

Member, Organizing Committee, Teaching Workshop, held in Inverness in July 1993, International Union of Physiological Sciences.
Member, Planning Committee for Australian Neurosciences conference to be held in Sydney in Feb 1994.
Member, Planning Committee for meeting in Shanghai in Nov 1993 on the use of computers in education, International Union of Physiological Sciences.
Official of international scientific society

International Union of Physiological Sciences: Deputy Chair, Commission on Teaching.

Significant University and external appointments

Associate Dean, Faculty of Medicine (1991-1994).  (From 1994, Associate Dean, Curriculum Planning).
Member, N.S.W. Board of Studies, Applied Studies (Higher School Certificate subject).
Consultant in vision and development, Sydney Eye Hospital.
Policy Committee, Graduate Australian Medical Schools Admission Test and Co-Chair of the Science group.
Assessor for promotions to Associate Professor/Reader, Univ. of Western Australia and Univ. of Queensland. 
Member, Neuroscience Panel, Univ. of Kuwait Medical School.
Educational consultant, Committee for Advancement of University Teaching.
Service to University and Department (and community)

Advice on courses and careers: at career days arranged by the University.
Presentation for Centre for Teaching and Learning on postgraduate supervision.
News media

Supplied information on the four-year postgraduate medical degree, medical communication and on medical research funding. THESES PASSED in 1993

PhD

Dixon G (1993) Development of the dorsal lateral geniculate nucleus and
geniculocortical pathway.
BSc(Hons) (Co-supervised with P.R. Martin) Ghosh K (1993) The morphology of retinal ganglion cells in the marmoset monkey. (Result: 1st class, Colin Dunlop Prize) BSc(Med)(Hons) (Co-supervised with B. Dreher) Hansen B (1993) Gradients in the developing superior colliculus. (Result: 2nd class, division 2)
5-YEAR RESEARCH PUBLICATIONS

JOURNAL ARTICLES

1989

Gayer, NS, Horsburgh GM, Dreher B (1989) Developmental changes in the
pattern of retinal projections in pigmented and albino rabbits. Developmental
Brain Research, 33, 315-332

Sefton AJ, Dixon G, Lund RD (1989) Cross-species retinal transplantation to the central nervous system. Transplantation Proceedings, 21, 3169-3170

1990

Huxlin KR, Tuch BE, Sefton AJ, Dixon G (1990) Grafting of fetal pancreata into neonatal rat brain. Transplantation, 49, 857-861

Warton SS, Perouansky M, Grantyn R (1990) GABAergic synaptic connections in cultures from the rat superior colliculus. Developmental Brain Research, 52, 95-111

1991

Dixon G, Sefton AJ (1991) Ganglion cell survival in embryonic rabbit retina transplanted to the midbrain of neonatal rats. Experimental Brain Research, 86, 182-189

Sefton AJ, Dreher B, Lim W-L (1991) Interactions between thalamic, callosal and associational projections to the visual cortex of the developing rat. Experimental Brain Research, 84, 142-158

1992

Huxlin KR, Sefton A Jervie, Furby J (1992) A technique for the explantation of mammalian retina on to the chorio-allantoic membrane of the developing chick. Journal of Neuroscience Methods, 41, 53-64

Huxlin KR, Sefton A Jervie, Furby J (1992) The origin and development of retinal astrocytes in the mouse. Journal of Neurocytology, 21, 530-544

Langford C, Sefton A Jervie (1992) The timecourse of axonal loss from the developing optic nerve of the guinea-pig is consistent with that of other mammals. Visual Neuroscience, 9, 555-564

1993

Hankin M, Sefton, A Jervie and Lund, RD (1993) Spatial and temporal patterns of transplant-derived retinal axon outgrowth in neonatal cerebral cortex. Developmental Brain Research, 75, 146-150 

Huxlin KR, Sefton A Jervie, Schulz M, Bennett MR (1993) Effect of proteoglycan purified from rat superior colliculus on the survival of murine retinal ganglion cells. Developmental Brain Research, 74, 207-217

CHAPTER IN BOOK



Sefton A Jervie, Dreher B (1994) The visual system. The Rat Nervous System: A Handbook for Neuroscientists, 2nd Edn, Paxinos G, ed, Academic Press, Sydney (in press)





ARTICLES RELATING TO TEACHING AND ADMINISTRATION



1990

Sefton A Jervie (1990) Selection of medical students. Medical Journal of Australia, 153, 440-441



Sefton A Jervie (1990) Selection into the Faculty of Medicine. Medical Scripts, 2.1, 3-6



1991

Sefton A Jervie (1991) Experiments in neuroscience. A Sourcebook of Practical Experiments in Physiology Requiring Minimal Equipment, International Union of Physiological Sciences, World Scientific Publications, Singapore, 23-37



Sefton A Jervie (1991) Studying medicine at The University of Sydney. Careers in NSW (August) 



Sefton A Jervie (1991) Communication in medical practice. Medical Observer (Nov), 31



1992

Sefton A Jervie (1992) Whither practical classes? Advances in Physiological Sciences, Macmillan India Ltd, New Delhi, 24-30



Sefton A Jervie (1992) A graduate degree for medicine at The University of Sydney. New Doctor, 57, 21-22



Armstrong R, Sefton A Jervie (1992) Selection process into medicine. The Crossexaminer, 1, 11-13



Sefton A Jervie (1992) A postgraduate degree in Medicine. Medical Scripts, 4.1, 1-2



Sefton A Jervie (1992) Admission Update. Medical Scripts, 4.1, 4-5



Sefton A Jervie (1992) Studying Medicine at Sydney University. Nous,1.1, 2



Sefton A Jervie (1992) Women in Medicine. Nous, 1.3, 3



Sefton A Jervie (1992) A new medical curriculum at the University of Sydney. Nous, 2.2, 3



1993

Sefton A Jervie (1993) Changes in medical education at the University of Sydney. ANZAME Journal



Sefton A Jervie (1993) Medical education in Australia: new perspectives. Ulitarra, 4, 86-92



Sefton A Jervie (1993) Implementing a four-year postgraduate curriculum. Medical Scripts, 5, 1-3



Early 1994

Hayes S, Farnill D, Sefton A Jervie (1994) Improving the English language skills of preclinical medical students. Annals of Medical Education (in press)



Geffen L, Saunders N, Sefton A Jervie (1994) A progress report on Australian  graduate medical schools. Medical Journal of Australia (in press)



Sefton A Jervie (1994) The Harvard experience: a graduate medical program. Sydney University Medical Journal (in press)



Sefton A Jervie, Somjen G (1994) The International Teaching Workshop in Inverness, 1993. Advances in Physiology Education (in press)





BOOK EDITED



Sefton A Jervie, Cheng N, Thong IG, eds (1992) The Centenary Book of the Medical Society, University of Sydney. Hale and Iremonger, Sydney, 266pp





REPORTS in 1993



Annual Report and Profile of entrants: Admission to the Faculty of Medicine (May)

Report to Dean of Education, Harvard Medical School: The Harvard course in Human Nervous System and Behaviour (Dec)



(with G Somjen) Report to participants and the International Union of Physiological Sciences on the 1993 Inverness Workshop for Teaching Physiology (Dec)





CONFERENCE ABSTRACTS AND PRESENTATIONS in 1993

RESEARCH-RELATED

Huxlin KR, Sefton A Jervie, Carr R, Schulz M, Bennett MR (1993) Collicular chondroitin sulphate proteoglycan prevents the natural death of retinal ganglion cells in situ. Proceedings of the Australian Neuroscience Society, 4, O13-3, Melbourne (Feb)

Tevah LV, Fitzgibbon T, Sefton A Jervie (1993) What is the anatomical relationship between the thalamic reticular nucleus and the thalamus? Proceedings of the Australian Neuroscience Society, 4, 16, Melbourne (Feb)

Tevah LV, Fitzgibbon T, Sefton A Jervie (1993) Photic responses of the LGN used as a stereotaxic guide for micropipette placement. Proceedings of the Australian Neuroscience Society, 4, 70, Melbourne (Feb)

Hanson B, Dreher B, Keay K, Sefton A Jervie (1993) Spatio-temporal pattern of maturation in the superior colliculus. Proceedings of the Australian Neuroscience Society, 4, 81, Melbourne (Feb)

Armson P, Huxlin KR, Nichol KA, Schulz MW, Sefton A Jervie, Bennett MR (1993) Retinal ganglion cell survival can be maintained in vitro by a thalamically derived factor distinct from that isolated from the superior colliculus. Proceedings of the Australian Neuroscience Society, 4, 84 (Feb)

Dixon G, Sefton A Jervie (1993) Development of GABA-immunoreactivity in neurons of the rat dorsal lateral geniculate nucleus. Robertson Symposium, Canberra (Feb)

Sefton A Jervie (1993) Growth and development of the brain. Symposium on ageing in the brain. Australian Geriatrics Society and Royal Australian College of Physicians, Sydney (Apr)

Huxlin KR, Armson P, Sefton A. Jervie, Nichol K, Schulz M, Carr R, Bennett MR (1993) Molecules carrying the HNK-1 epitope act as specific trophic factors in the developing mammalian nervous system. International Union of Physiological Sciences, Abstracts 138.3, Glasgow (Aug)

RELATED TO TEACHING AND ADMINISTRATION

Hayes S, Farnill D, Sefton A Jervie (1994) Improving the English language skills of preclinical medical students. Network Meeting of Community-Oriented and Problem-Based Medical Schools, Sherbrooke, Canada (Aug)