ProfessorMark Gillies

Project Opportunities
Title: Müller glial-neuronal-vascular interactions in retinal vascular diseases

Summary of opportunity:

Research projects in the Macular Research Group are focused on the cellular and molecular mechanisms of Müller glial-neuronal-vascular interactions in retinal diseases. The group has made significant contributions to modelling retinal disease both in vivo and in vitro, and has recently successfully constructed a transgenic mouse in which Müller cells can be specifically targeted using a Cre-Lox system in order to study the role of Müller cell dysfunction in retinal disease. The results of this study have been published in Journal of Neuroscience (Shen W et al. 2012;32:15715-15727).

Opportunity synopsis:
Possibly because they are invisible to clinical examination, the role of Müller cells in the pathogenesis of retinal diseases is very poorly understood. Providing the main nutritional and regulatory support to retinal neurons and vascular cells, Müller cells are both a target and a potential key player in retinal diseases such as diabetic retinopathy, macular telangiectasia type 2 and retinal veno-occlusive disease. Precisely how Müller cell dysfunction results in retinal neuronal damage and blood-retinal barrier breakdown has not yet been established. We hypothesise that Müller cell dysfunction is a major contributor to neuronal injury and blood-retinal barrier breakdown in retinal diseases.We have recently generated an inducible transgenic line in which a Müller cell-specific promoter along with a Cre/Lox-P approach was used for Müller cell-specific gene targeting (Shen et al. 2012). Crossing this transgenic line into transgenic mice carrying an attenuated form of the diphtheria toxin fragment A (DTA176) gene led to conditional Müller cell ablation, which was followed by photoreceptor apoptosis, blood-retinal barrier breakdown and, later, intraretinal neovascularisation (Shen et al. 2012). We will use this unique transgenic line to study the cellular and molecular mechanisms underlying Müller glial-neuronal-vascular interactions in this novel transgenic model and effort will be taken to test novel strategies for neuroprotection and inhibition of blood-retinal barrier breakdown. We expect that a better understanding of the role of Müller cells in retinal disease will result in improved approaches to the prevention and treatment of retinal diseases. The Macular Research Group, which includes a clinical research unit as well as the laboratory, is well positioned and experienced in translating basic science discoveries into improved clinical outcomes.