VISION DEVELOPMENT LABORATORY

Ann E. Sefton

  

  

RESEARCH

PERSONNEL in 1994 and 1995

Dr Ann E. Sefton Professor from 1992 (in-charge) (0.2)
Associate Dean, Curric., Fac. Med.
University 1974-
1994
Dr Ann Goodchild Research Assistant, Grade 2
(with Paul Martin)
NHMRC 1992-
Paul Armson PhD student (0.25) 1991-
Krystel Huxlin PhD student
Postdoctoral Fellow
APA
Fac. Med. Award
1990-94
1994
Amanda Johnston BSc(Med) (Supervisor:
Bogdan Dreher, Anat. & Histol.)
1994
Nick Barrett BSc(Med) (Assoc. Supervisor:
Brendan O'Sullivan, RPAH)
1994

Affiliate:
Dr Tom Fitzgibbon Dept of Clinical Ophthalmology (0.2) 1990-

Current effective full-time personnel = 1.4

  
The research of the Laboratory is principally directed towards understanding the phenomena taking place during 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 pathway in adult primates.
  

PROJECTS in 1994

The role of trophic factors in the survival of injured adult neurons

Neurons in the adult mammalian central nervous system degenerate following traumatic lesions such as axotomy. Whether their survival depends on the availability of a developmentally regulated trophic factor produced by their target cells is not known. Experiments were continued to test this hypothesis by applying the 480 kDa superior collicular chondroitin sulfate proteoglycan, purified in the Laboratory of Max Bennett, to adult rat retinal ganglion cells following their axotomy. When injected intraocularly for two weeks following intraorbital section of the optic nerve (which destroys 80% of retinal ganglion cells within two weeks), this proteoglycan prevented the degeneration of 64% of the injured retinal ganglion cells. This saving effect was larger than that of any other known trophic factor tested in the same system. Our results indicate that adult rat retinal ganglion cells may revert to a 'development-like' state following axotomy. This would include a renewed dependence on target-derived trophic factors for survival.

Glial response to axotomy and the application of trophic factor

This project was undertaken in collaboration with Zofia and Bogdan Dreher from the Dept of Anatomy. It has been postulated that the major reason for the lack of regeneration following a lesion in the mature mammalian central nervous system is that its glial environment becomes inhibitory to axonal regrowth as a result of the injury. Part of this inhibitory glial response consists of an astrogliosis in which astrocytes hypertrophy, multiply and express high levels of GFAP. The aim of this study was to characterize the glial response to section of the optic nerve, intraocular penetrations (the method of choice for intraocular injection of therapeutic substances) and intraocular injections using a battery of antibodies recognizing proteins specific to the two types of macroglia in the rat retina - astrocytes and Müller cells. The findings were rather startling: in the retina, unlike the rest of the brain, there was no astrogliosis in response to the Wallerian degeneration of retinal ganglion cells or intraocular penetrations. When collicular proteoglycan was injected into the eyes, however, the expression of GFAP in astrocytes decreased markedly so that the cells were no longer visible. Rather than astrocytes being stimulated by injury, it was the Müller cells that increased their expression of GFAP and a range of other proteins. The responses of Müller cells were stronger following intraocular injections of collicular proteoglycan than as a result of the Wallerian degeneration of 80% of retinal ganglion cells. It was concluded that the retina is a unique region of the central nervous system in terms of its glial response to injury. Müller cells, rather than astrocytes, became reactive in response to changes in their immediate environment.

Neuronal response to axotomy and the application of trophic factor

In collaboration with Zofia Dreher, Bogdan Dreher and Max Bennett, the reaction of retinal neurons and glia were assessed after section of the optic nerve followed by the intraocular injection of the collicular chondroitin sulfate proteoglycan which was shown to rescue a significant proportion of adult retinal ganglion cells from axotomy-induced cell death. A battery of antibodies were used to monitor the levels of various intracellular proteins such as protein kinase C, the calcium binding proteins calbindin and parvalbumin, and neurofilaments. Protein kinase C is thought the be involved in the pathway controlling cell death while a failure of intracellular calcium regulation (which involves the use of calcium binding proteins) has been demonstrated to kill neurons. The aim was thus to determine how the levels of such molecules change in retinal neurons (particularly retinal ganglion cells) following axotomy and the injection of collicular proteoglycan. This may enable us to predict how well equipped retinal ganglion cells are to survive axotomy and which intracellular pathway the trophic collicular proteoglycan is activating to rescue them. This study is still ongoing.

The identification of neurons exhibiting NADPH-diaphorase activity in the normal adult rat retina

NADPH-diaphorase is an enzyme that has been co-localized with nitric oxide synthase. It was found in our laboratory that using better controlled fixation parameters, this enzyme could be detected in many more retinal cells than was previously published. NADPH-diaphorase was identified in ganglion cells, displaced amacrine cells, amacrine cells in the inner nuclear layer, photoreceptors and Müller cells of the normal adult rat retina. This was also the first time that a glial cell was found to contain a constitutive form of nitric oxide synthase. These results have important implications for the role of nitric oxide in normal retinal function, suggesting that this molecule may act as a neuromodulator in the light transmission pathway. In addition, given the reactivity of Müller cells following damage to the retina or optic nerve, nitric oxide may also play a role in retinal pathology.

Changes in the expression of NADPH-diaphorase in the adult rat retina following axotomy

This project was carried out in collaboration with Max Bennett. One hypothesis as to the mechanism of neuronal cell death following axotomy in the central nervous system is that microglial cells which invade the injury site and phagocytose debris from dead cells, also produce nitric oxide to kill live but inactive neurons. Astrocytes in the brain have also been shown to express inducible nitric oxide synthase after cerebral damage such as that resulting from stab wounds or ischaemia. In addition, previous results from this Lab have suggested that retinal Müller cells normally expressed NADPH-diaphorase. Therefore, it was of interest to determine whether any of these cell types express NADPH-diaphorase in the retina following section of the optic nerve and thus, whether they could contribute to the massive ganglion cell death which occurs within two weeks of axotomy. It was found that two weeks following section of the optic nerve, no microglia or astrocytes were labelled for NADPH-diaphorase. However, there was an increase in the staining of Müller cells. Therefore, in the retina, it is unlikely that astrocytes and microglia use nitric oxide to kill injured retinal ganglion cells following axotomy. It is also uncertain whether nitric oxide acts as a toxic molecule in the retina since injections of L-NAME, an inhibitor of nitric oxide synthase, did not result in the rescue of retinal ganglion cells following axotomy. Preliminary results suggest that the injection of collicular proteoglycan caused an increase in the expression of NADPH-diaphorase in the retina, both in Müller cells and a neuronal population in the ganglion cell layer, suggesting that in this situation, rather than being toxic to injured neurons, nitric oxide may actually contribute to their survival.
  

RESEARCH PLANNED for 1995

Collaborative work with Paul Martin will continue in studies of the visual system of the marmoset. In addition, a new collaboration with Max Bennett 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 ganglion 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. A study of the thalamic reticular nucleus in the cat is being prepared for publication.
  

COLLABORATIONS

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

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

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 neuroanatomical tracing techniques; laminar flow cabinet; incubator; surgical, anaesthetic and some electrophysiological equipment; Macintosh personal computers and accessories.
  

THESES PASSED in 1994

PhD

Huxlin KR (1994) Effect of collicular factor on the development and regeneration of rat retinal ganglion cells.

BSc(Med)(Hons)

Barrett N (1994) Neuroanatomy of working memory and attention: Study using position emission tomography. (Assoc. Supervisor: Brendan O'Sullivan, Royal Prince Alfred Hospital. Result: 1st Class)

Johnston AJ (1994) The spatio-temporal pattern of synapse formation in the superior colliculus of perinatal albino rats. (Supervisor: Bogdan Dreher. Dept of Anatomy & Histology. Result: 1st Class)
  

OTHER RESEARCH ACTIVITIES in 1994

Departmental reviews

John Curtin School of Medical Research, A.N.U.

Dept of Physiology & Pharmacology, Univ. of Queensland (Chair).

Dept of Psychology, Univ. of Sydney.

Refereeing

Manuscripts: for Journal of Neurocytology (2).

Grant (and fellowship) applications: National Health and Medical Research Council (4), Australian Research Council (2), Department of Industry, Technology and Commerce (2), Committee for the Advancement of University Teaching (3), Lions Clubs Foundation (1), Ramaciotti Foundation (1).

Conference organizing committees

Member, Planning Committee for Australian Neurosciences conference, Sydney (Feb).

Member, Planning Committee, meeting on computer-based education, Federation of Asian & Oceanian Physiological Societies, Shanghai (Nov).

Official of international scientific society

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

Significant University and external appointments

Consultant in vision and development, Sydney Eye Hospital.

Assessor for promotions to Assoc. Prof./Reader: Univ. of W.A. and Univ. of Queensland.

Member, Neuroscience Panel, Univ. of Kuwait Medical School.

Sep 1993-Jan 1994: Visiting Professor, Harvard Medical School, USA.

Service to University

Presentations for Centre for Teaching and Learning on postgraduate supervision and on publishing in the sciences.

Public Lecture (on vision), Faculty of Science, (Aug).

News media

Supplied information on various issues including medical research funding, growth factors in development and the graduate medical program at Univ. of Sydney, including research opportunities.
  

5-YEAR RESEARCH PUBLICATIONS

MOST RECENT TOTAL ANNUAL CITATIONS (for 1993): 81

  

FUNDING in 1994 and 1995

NHMRC The visual system in dichromatic and
trichromatic marmoset monkeys
(*Lab's share annually (30% = $18,400)
Martin PR 1993
Sefton A 1994 *$61,334
1995 *$61,334

Total for 1994: $18,400

Total for 1995: $18,400

  

  

TEACHING

5-YEAR PUBLICATIONS RELATED TO TEACHING AND CURRICULUM DEVELOPMENT

Journal Articles

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

Sefton A Jervie (1991) Selection of medical students. The Sydney experience. Radius Annual, 1, 18-19

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 (1993) Decision-making for major educational change: A four year postgraduate medical curriculum at the University of Sydney. ANZAME Bulletin, 20, 3-10

Sefton A Jervie (1993) Why change medical education to a four-year postgraduate programme? Ulitarra, 4, 86-92

Geffen L, Saunders N, Sefton A Jervie (1994) Australian graduate medical schools: A progress report. Medical Journal of Australia, 160, 393-394

Sefton A Jervie (1995) Medical education in a time of change: A view from the University of Sydney. Medical Education (in press)

Sefton A Jervie (1995) Educating the health workforce in customer focus. Proceedings of the Customer Focus Conference (in press)

Book Edited

Sefton A Jervie, Cheng N, Thong IG, eds (1992) The Centenary Book of the Sydney University Medical Society, Hale and Iremonger, Sydney, 224pp. (Includes contributions to Chapters 2, 4, 5 and 7).

Chapters in Books

Sefton A Jervie (1991) Experiments in neuroscience. A Sourcebook of Practical Experiments in Physiology requiring Minimal Equipment, International Union of Physiological Sciences, ed, World Scientific, Singapore, 47-74

Sefton A Jervie (1992) Whither practical classes? Advances in Physiological Sciences, Manchanda SK, Selvamurthy W, Mohan Kumar V, eds, M/S Macmillan India, New Delhi, 24-30

Hayes SC, Farnill D, Sefton A Jervie (1994) Improving the English communication skills of preclinical medical students. Annals of Community-oriented Education, Engel C, Schmidt H, Vluggen PI, eds, 7, 317-328

Conference Abstract and Presentation

Sefton A Jervie, Somjen, G (1994) Workshop on Teaching, International Union of Physiology Sciences, Advances in Physiology Education, 11, S70-S77, Inverness (Jul 93)
  

COURSES TAUGHT

Medicine 3

Lectures: 23 in the Neuroscience course.

Prac. classes: 5, each 2 h, presented twice (= 20 h).

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

Tutorials: 5 revision, each of 2 h (= 10 h).

Medical Science 3/Science 3: Advanced Neurosciences

Lectures: 2, on plasticity and development.

Practical classes: 2, of 2 h.

Seminars/assessment: Was based on student's presentation of a 3 h seminar.

STUDENT CONSULTATIONS

As Associate Dean in the Faculty of Medicine, throughout the year, help was given to medical students as well as to those seeking admission to Medicine. Assistance was offered to students in all courses taught.

*SPECIAL STUDIES PROGRAM

As Visiting Professor, Harvard Medical School, Office of Educational Development (Jan).
  

TEACHING HOURS in 1994

Med 3 Sc 3 Total
Lectures 23 2 25
Practical classes (no.) 10 (10) 2 (4) 14
Demonstrations 3 (12) - 12
Tutorials 6 (13) - 13

Total formal contact teaching time = 64 h

  

  

ADMINISTRATION

(see also OTHER RESEARCH ACTIVITIES in 1994)

Appointment

Associate Dean, Curriculum Development, with responsibilities for developing the Graduate Medical Program for the Faculty of Medicine.

Curriculum design

BMedSc degree: Member of the committee for the core course 'Human Life Sciences 2'.

New medical degree: Chair of the Curriculum 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.

Reports relating to teaching

Admissions to the Faculty of Medicine (profile of 1994 entrants).

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

Graduate Medical Program Planning Papers 1, (authored and edited), 2 and 3 (authored).

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.

Report on the computer-Aided Teaching Workshop, Shanghai (Nov).

Review Committees

Chair, Review of Dept of Physiology and Pharmacology, Univ. of Queensland (May).

Member, Review team for John Curtin School for Medical Research (Apr).

Member, Review team for Dept of Psychology (Sep).

Invited speaker

Univ. of N.S.W., Dept of Physiology (Mar).

Royal North Shore Hospital Workshop (Mar).

Workshop Leader on Problem-based Learning in Paediatrics, Westmead Hospital (Apr).

Consortium of Graduate Medical Schools Workshop, Brisbane (Apr).

Careers Teachers Conference, Univ. of Sydney (Jun).

Workshop, Faculty of Education, Univ. of Sydney (Jul).

NSW Dept of Health, Customer-focus in medical education, Opera House (Nov).

External Examiner

Division of Physiology, Dept of Basic Medical Sciences, Univ. of Papua New Guinea (Nov).

University committees

Member, Advisory Committee, Learning Assistance Centre.

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

Member, Save Sight Foundation.

Academic Board

Active member.

Member, Broadway Review Committee.

Chair, Examinations, Assessments and Related Subjects.

Representative of the Chair on appointments/ promotions committees.

One of a small committee that interviewed Deans during the preparation of Quality materials.

Faculty of Medicine

Associate Dean (Curriculum Development) (from Jan) and member ex officio of its various committees and subcommittees.

Responsible for Faculty's submission to the Quality Round.

Member, Dept of Clinical Ophthalmology.

Chair, Boards of Examiners for BSc(Med)(Hons).

Chair, Admissions Committee for UMP.

Member, various appointment committees.

Member (ex officio), Dean's Planning and Advisory Committee.

Member (ex officio), Faculty Management and Advisory 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 (ex officio), 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.

Workshops

Chair or speaker at Workshops for the Faculty of Medicine Graduate Medical Program: Mar, Jun, Jul, Aug, Dec.

Conference organizing committees

Member, Planning Committee for Computer-Aided Teaching workshop in Shanghai on the use of computers in education, for Federation of Asian and Oceanian Physiological Sciences. Acted as Instructor at the workshop (Nov).

Official of international scientific society

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

Significant University and external appointments

Consultant in vision and development, Sydney Eye Hospital.

Sydney representative, Policy Committee, Graduate Australian Medical Schools Admission Test.

Member, Neuroscience Panel, Univ. of Kuwait Medical School.

Educational consultant, Committee for Advancement of University Teaching.

Service to University and Department

Advice on courses and careers at career days arranged by the University.

Presentation for Centre for Teaching and Learning on postgraduate supervision.

Service to community

Member, Gladys Leach Award Committee, North Sydney Girls' High School.

News media

Interviews and information on the four-year postgraduate medical degree and medical careers: The Bulletin, The Australian, Northern Herald, Sydney Morning Herald (twice), Telegraph Mirror, ABC Radio Perth.