High-Frequency Ultrasound Imaging of the Duck Embryo Retina as a Near Real-time Preclinical Platform to Study Advanced Proliferative Diabetic Retinopathy
3 minute read
One of the most common diabetic complications is diabetic retinopathy (DR), a condition that affects the blood vessels in the retina and is the leading cause of vision impairment in working-age adults worldwide. There is a need for a suitable preclinical animal model that allows researchers to quickly and easily study DR such that new therapies may be developed and tested. Here we propose a near real-time platform that uses the duck (Anas platyrhynchos domesticus) embryo retina and basic commercially available medical ultrasound to observe and study advanced PDR ex ovo.
In more progressive stages of DR, or proliferative DR (PDR), new vessels form on the retina to make up for this weakened original vessels. The formation of new vessels is a serious issue as they are not as robust as natural retinal vessels, and are considerably more prone to bursting, which can cause significant vision damage, or in extreme cases, blindness.
Previously, Shi et al. used the chicken (Gallus gallus domesticus) embryo injected with Streptozotocin (STZ) as a model for type-I diabetes in 2014. Shi and colleagues observed changes in the retina between healthy and diabetic embryos via tissue histology. Their experiments were conducted in ovo, making it difficult to manage microinjections and to examine the retina. Additionally, it does not allow direct, near real-time in vivo assessment of retinas as embryo retinas must be harnessed for histological analysis.
Similar to the chicken eye, the duck eye itself is large compared to its body size, allowing for easy research accessibility. Its retina is also cone-dominant, making it a suitable candidate for studies modeling the human eye. Additionally, the homogenous response to damage between avian retinas and human retinas makes it a favourable animal model for studies in retinal diseases. The retinas and photoreceptors of the duck embryo also exhibit similar structures as the chicken eye. Furthermore, the duck embryo follows a slightly slower embryonic development cycle than the chicken, allowing researchers more time to study the retina during critical periods. Both embryo models are excluded from ethics committee approval because they are not considered animals.
Currently, rodents, dogs, and zebrafish models are used for DR research. However, these models have significant limitations. From fundamental physiological retinal differences to humans, to experiments being highly resource-intensive, a better animal model is desired. The development of this platform could be used for evaluation of novel anti-VEGF or anti-angiogenic drugs or therapeutic agents for advanced DR over a treatment period. Because of the cheap experimental capability of avian embryo models (<$1 per egg), as well as the use of widely accessible medical ultrasound machines instead of advanced retinal imaging modalities, this will be a cost-efficient method to study DR. This also acts as an example for future studies of other eye diseases in avian embryos. Other advantages include the embryos’ reduced ability to feel discomfort during manipulation and shorter experiment turnover time.
Please find the slides here.