My group’s interests focus on understanding the molecular mechanisms which lead to retinal vascular diseases. The focus of our research is to understand the role that nitric oxide synthase (NOS) isoforms and oxidative stress pathways play in retinal degeneration and in subsequent pathological angiogenesis. In particular, we are interested in using gene delivery strategies and transgenic models to study the pathologies associated with retinal vasculopathy.
Current research projects
My current research interests fall into three main themes:
i) Role of NO and oxidative stress in diabetic vascular disease
In the healthy vasculature normal homeostasis is maintained by the vasodilator nitric oxide (NO) produced from endothelial nitric oxide synthase (eNOS). Diabetic vascular disease, however, is characterized by endothelial dysfunction and a reduction in the bioavailability of NO. In the eye the reduced production of NO also contributes to apoptotic cell death and capillary closure; initiating a cascade of events leading to the sight threatening proliferative stage of diabetic retinopathy. My group is investigating the mechanism via which diabetes affects NO mediated signaling with the ultimate aim to identify interventions which can prevent the severity of diabetic vascular disease.
ii) Role of inflammatory cytokines in ischaemic retinopathy
Intravitreal neovascularisation (NV) is a serious complication of diabetic retinopathy and retinopathy of prematurity with uncontrolled vessel growth resulting in severe vision loss. In collaboration with Dr Tom Gardiner my group is currently investigating the mechanism via which TNF? depletion facilitates intra-retinal neovascularisation. Our long term goal for this project and the project outlined below is to understand why retinal vessels fail to revascularise the ischemic retina.
iii) Role of NO and reactive oxygen species in developmental and pathological retinal angiogenesis
Nitric oxide (NO) plays a crucial role in the regulation of retinal neovascularisation and in the retina is derived from one of several nitric oxide synthase isoforms. There are significant differences in the regulation of each NOS isoform and we are currently using molecular strategies to understand how the NOS isoforms are regulated to facilitate normal vascular development and how this regulation is affected in pathology. This work also encompasses a study of the role that NO plays in the establishment and maintenance of endothelial-glial and endothelial–mural cell interactions. The ultimate aim of this work is to identify novel therapeutic targets which will promote intra-retinal recovery.