Dr. Sarabjit Kaur Saggu
MBBS, PGDHA, PGCCPsy, PhD (Medicine)
South Australian Institute of Ophthalmology
Level 8, East Wing
Royal Adelaide Hospital
North Terrace
Adelaide
South Australia 5000
eye@health.sa.gov.au
Bachelor of Medicine and Surgery (SP University, India)
Post Graduate Diploma in Health Administration (IHCA, India)
Post Graduate Certificate Course in Psychiatry and Psychosexual Medicine
(IMA, India)
PhD in Medicine, undergoing (The University of Adelaide, Australia)
Member Asutralian Neuroscience Society
Member Australian Society of Medical Research
Member Australasian Society of Brain Research
Optic nerve damage
Topic- The spatiotemporal pattern of optic nerve degeneration after intraocular excitotoxic injury.
This study is about the changes occurring in the optic nerve after excitotoxic insult to the RGCs. Its objective is to elucidate the mechanism underlying ascending optic neuropathy secondary to excitotoxic RGC injury in order to provide basis for the role of anti-excitotoxic agents as neuroprotectants for the optic nerve. The research commenced because efforts to prevent and cure RGC injury and optic nerve degeneration have proven inadequate to address the problem of preventable causes of vision impairment.
Two major theories describe the mechanism and pathogenesis of any nerve degeneration. The Wallerian degeneration involves distal stump of the nerve in response to acute focal axonal damage (such as axotomy). Whereas, slowly evolving Wallerian-like dying-back axonopathy occurs as a result of more chronic stress to either the axon or the cell body and is associated with many inherited, metabolic, malignancy-related and drug-induced neurotoxicities. Although, various toxin-induced models are used to study dying back axonopathy, none of the studies have considered the use of NMDA, an excitotoxic agent, to produce cell death and possible dying-back degeneration.
It is important to study the mode of nerve degeneration after excitotoxicity because excitotoxicity plays an important role under physiological and in many pathological conditions such as acute seizure, ischemia/ stroke, hypoglycaemia, Huntington’s disease, HIV encephalopathy, Parkinson’s disease, Alzheimer’s disease and many other metabolic conditions. Possibility of the role of excitotoxic neurotransmitter has also been considered in eye conditions such as glaucomatous, ischaemic and other retinopathies. The mechanism of excitotoxic neuronal cell death by the stimulation of NMDA receptors is well established. However, the mode of axonal degeneration secondary to excitotoxic somal death is unknown.
The models of dying back degeneration used so far have not made it clear where the primary of insults is and the systemic toxins could have damaged nerve fibres and cell bodies directly. However, the method design for this study will be based on the NMDA model of RGC injury. This will be a perfect model of exclusive cell damage where the hypothesis of dying back axonopathy after somal injury can be tested. The methods used will be easily reproducible and will be based on the application of standard procedures with some modifications in a planned manner.
The research aims primarily to explore the morphological, immunological and genetic changes in the retina and the optic nerve fibres secondary to intravitreal injection of NMDA. Light microscopic and ultrastructural changes in the retina and different levels of optic nerve fibres (optic tract, intracranial and intra-orbital part) will be studied at various time-points. Immunohistochemistry will focus on the expression of NF-L, GFAP, ED-1, NMDA-R1, ion channel and various adhesion molecules in the nodal and paranodal regions of myelinated axons. Simultaneously, alterations in gene expression at RGC level will be correlated with ultrastructural and molecular derangements of axonal, glial components and axo-glial relationships changes at various levels in the optic nerve axons.
The results of the study will be utilised to develop the mechanism of optic nerve degeneration secondary to excitotoxic RGC injury. This study will also help us understand the pathogenesis of chronic neurodegenerative conditions and peripheral neuropathies better. Moreover, the results will try to explain the therapeutic role of anti-excitotoxic drugs as a mean of preventing nerve degeneration in all those clinical conditions where excitioxicity plays a major role in RGC damage.