A Study Of The Role Of Voltage-gated Potassium Channels In The Process Of Phototransduction, In The Setting Of Photoreceptor Sensitivity Levels And Response Times, And In The Progression Of A Distinctive Form Of Inherited Retinal Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$360,371.00
Summary
Inherited retinal disease is a major cause of blindness but the genetic basis is extremely heterogeneous. One such disorder, cone dystrophy with supernormal rod ERG, arises from mutations in KCNV2 that encodes a potassium voltage-gated channel protein. The objective of the project is to use animal models of the disease to determine the role of this channel protein in normal visual function and to assess the impact of loss of function on retinal development and function.
The Role Of Dopamine And Other Neuromodulators As Light Signals In The Inner Retina: A Link To Night Blindness Disorders
Funder
National Health and Medical Research Council
Funding Amount
$250,250.00
Summary
Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-ligh ....Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-light switch can have fatal consequences. Night blindness is a symptom characterised by reduced vision in the dark and slow adaptation to dim light. Some congenital night blindness disorders are caused by mutations in the photoreceptor calcium channels which mediate signal transmission. Additionally, patients treated with neuroleptics, a group of drugs which affect the dopaminergic system, suffer night vision disorders. Dopamine acts as a light signal in the retina. AII amacrine cells are pivotal neurones for night vision segregating two channels (ON and OFF) which convey visual information. AII cells are modulated by dopamine and thus, represent interesting targets to study the role of dopamine in the dark-light switch. Much is know about the action of dopamine on transmission of ON signals channelled by AII cells. However, its action on the OFF channel is largely unknown. We believe that some night vision disorders originate by imbalance in the dopaminergic system in the retina and its effects on AII cells. We will test our hypothesis by studying the modulatory effect of dopamine on calcium dependent signal transmission between AII cells and their partners in the OFF channel. Our hypothesis will be further tested by using animal models in which dopamine receptor function is altered. The results of these studies will provide us with an invaluable model to understand the physiological basis of the dark-light switch and of the role of dopamine in night vision disorders.Read moreRead less
Discovery And Development Of Better Pain Treatments
Funder
National Health and Medical Research Council
Funding Amount
$9,613,850.00
Summary
Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clini ....Many forms of pain remain poorly treated, leading to significant quality of life and economic losses. This Program grant will discover and characterise new peptides from cone snails and spiders that modulate specific channels in nerves that are critical to the transmission of pain signals to the brain. Using advanced chemical and structural approaches, promising leads will be optimised for potency and stability and evaluated in disease and pathway-specific models of pain to establish their clinical potential.Read moreRead less
Determining The Mechanisms Underlying Chronic Visceral Pain And Providing Novel Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
Gastroenteritis activates special types of nerve endings in the gut to cause acute pain. In chronic gut pain, although the damaged tissue has healed, the nerve endings remain active and don’t reset back to normal. This project will identify why this occurs, determining pain mechanisms associated with Irritable Bowel Syndrome, a leading form of chronic pain. It will identify which ion channels and receptors can be targeted allowing the development of novel and effective therapies for pain relief.
Development Of Human Sensory Receptors Of The Inner Ear
Funder
National Health and Medical Research Council
Funding Amount
$418,281.00
Summary
Normal development of our special sense organs is crucial for sight, taste, hearing, and balance. The balance system mediates important postural and eye reflexes that are essential for movement and vision. Abnormal development of the balance system results in dizziness, vertigo, gait deficits, and impaired learning and reading ability in children. This study will investigate how the organs of balance mature and connect with nerve fibres of the inner ear during human development.
Ion Channels Underlying Inflammatory And Post-inflammatory Visceral Mechanical Hypersensitivity
Funder
National Health and Medical Research Council
Funding Amount
$453,439.00
Summary
Inflammation causes tissue damage that triggers ion channels within sensory nerve fibres to produce greater signals in response to mechanical events, causing acute pain. In chronic pain, although the inflamed tissue has healed, sensory nerve fibres fail to "reset" back to normal. Often chronic pain is more severe than acute pain. This project will identify which ion channels are responsible for signalling acute and chronic visceral pain, explaining why sensory nerve fibres fail to reset.