Development of new animal models for retinal degenerations
The Clear Vision Research Lab has developed and incorporated a range of rodent models of retinal degenerations. While there is no perfect model to simulate all the pathologies associated with human AMD, we use a growing number of approaches to better understand the progression of AMD and retinal degenerations in general. These models also serve to test the efficacy of novel AMD therapeutic and diagnostic pipelines, with a view towards commercialisation and R&D avenues.
The Clear Vision Research Lab light-damage model, otherwise known as photo-oxidative damage (PD), was developed in-house (Natoli et al. 2016) as a means to induce AMD-like disease in pigmented rodents. In this model rodents are exposed to a high intensity of light with the key benefits that both the oxidative stress and inflammation arms of AMD progression are targeted. The light-damage model has been recognised for its uniqueness and has fostered industry collaborations that have led to the model’s commercialisation and distribution around the world.
Transgenic Mouse Models
The Clear Vision Research Lab has access to the Australian Phenomics Facility (APF), which is a nationally funded facility dedicated to the development, characterisation and archiving of mouse models of human disease. This facility has experts in place to identify genetic traits that lead to a particular disease. Through the APF, we have the capacity to import and generate transgenic mouse lines to mimic various retinal degenerations in vivo. We currently have transgenic mouse lines that mimic retinal pigment epithelium (RPE) dystrophy, which leads to photoreceptor loss in the retina. The benefit of transgenic mouse models is that retinal degeneration often progresses slowly, which parallels the progression of human AMD. The protracted nature of retinal degeneration provides a unique view toward early diagnostic markers of AMD and long-term efficacy of novel treatment strategies.
The sodium iodate model of retinal degeneration is widely used in the research space and one that we have recently begun to use. In this model, mice receive a single dose of sodium iodate which selectively induces RPE cell death, in turn leading to AMD-like pathologies. The simplicity of this model makes it a useful tool for initial screens of novel therapeutics agents that may promote photoreceptor survival.
The Phoenix MICRON IV™ system (Phoenix Technology Group) is a specialized rodent optical coherence tomography (OCT) and fundus imager that can deliver laser-mediated photocoagulation. This process results in a localized choroidal neovascularisation (CNV) response in rodent retinas that mimics pathologies associated with wet AMD. The MICRON IV™ allows the us to monitor the development of a CNV response in vivo and in real time and directly observe the efficacy of potential therapeutic agents.
The oxygen-induced retinopathy (ROP) model is a useful model to study the effects of neovascular diseases of the eye, such as retinopathy of prematurity (ROP) and wet AMD. Neonatal animals present with normal retinal vascularisation ex utero, rather than the abnormal retinal vascular development observed in premature infants. The
ROP model takes advantage of the fact that by simply manipulating the environmental oxygen concentration, neovascularisation resembling that of premature infants can be induced and tightly controlled. This model provides us with a crucial tool to better understand ROP and test potential therapeutics together with the development of new medical devices.