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Oxidant Signalling Unit

Affiliated with the University of MelbourneUniversity of Melbourne Logo

Lead Researcher: Dr Hitesh Peshavariya

The Oxidant Signalling Unit at CERA develops approaches to improve treatment and outcomes for patients with ocular diseases. The key area of research is to investigate post-surgical glaucoma scarring and age-related macular degeneration (AMD). We are interested in translational approaches that include investigating the therapeutic potential of novel drugs and compounds using various animal models, tissue culture based experimentation and analysing patient-derived materials.

Current Research Projects

A non-cytotoxic approach to reduce ocular fibrosis

Wound healing is a classical response to any tissue injury repair and often leads to scar-forming fibrotic lesions. Post-surgical scarring response is a major problem that influences surgical outcomes in patients with eye diseases and can cause vision impairment and blindness. There are some non-selective cytotoxic drugs currently being used in clinic that exert serious side effects and lead to high recurrence rates of fibrosis and surgical failure. Hence, there is an immediate need to investigate safer and more effective therapeutic alternatives.

Chemical eye injuries are a condition of ophthalmic emergency that can produce extensive damage to the ocular surface and anterior segment of the eye and can lead to vision impairment. Early diagnosis and effective treatment can ensure best possible outcomes for this potentially blinding condition. First line of treatment comprises antioxidant vitamin C and topical steroid application to reduce inflammation and scarring. However, serious injuries often need longer treatment using these agents, which can cause corneal thinning and perforation.

We focus on investigating the post-operative/injury ocular scar formation by understanding the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-associated pathways in reactive oxygen species (ROS) production in post-surgical/injury ocular fibrosis. We aim to investigate how to improve long-term success of ocular surgery/injury and prevent/treat post-traumatic ocular scar formation and vision loss in the patients identifying novel targets.

 

Good cholesterol for treatment of AMD

Age-related macular degeneration (AMD) is a disease of the macula, and the leading cause of irreversible and severe central vision loss that occurs with aging. It is considered a major public health problem and a massive burden on health resources. The cellular pathology of AMD varies, but collectively, it affects the light sensitive photoreceptors within the retina and their supporting cells. The cause of AMD is not well understood but many theories are associated with mechanisms of oxidative stress, atherosclerotic-like changes, genetic predisposition and inflammation.

Hallmark features of early AMD include accumulation of lipid-rich cholesterol (bad cholesterol) termed ‘drusen’ underneath the retinal pigment epithelium (RPE), thickening of Bruch’s membrane (BM), and inflammation. There are currently no treatments to prevent the development of the early stages of AMD, nor specific interventions to prevent its progression to late AMD. However, increasing levels of high density lipoprotein (HDL) also known as “good cholesterol” has been shown to reduce the risk of the similar pathological conditions in cardiovascular diseases. However, the effects of HDL on AMD are unknown.

We hypothesise that reconstituted HDL (rHDL) treatment has protective effects and will slow or prevent BM thickening, inflammation and improve retinal function in mice. We explore the effects of rHDL using animal models with thickened Bruch’s membrane, lipid accumulation and inflammation. We are interested in testing the anti-inflammatory effects of rHDL in vitro using cell culture based methods.