New Approaches To Macular Degeneration: Test Tube Retinas
(Posted on Tuesday, January 24, 2023)
Age-related macular degeneration is a leading cause of blindness and affects over 196 million people worldwide. Despite its prevalence, very little is known about the causes or mechanisms of this disease. Now, researchers have engineered a new model of the retina that may help us develop a deeper understanding of macular degeneration, its causes, progression, and ultimately, how we might be able to treat the disease to prevent blindness.
One of the primary difficulties of studying age-related macular degeneration is that there are two forms of the disease: wet and dry macular degeneration. In dry macular generation, proteins and lipids accumulate beneath the retina of the eye. Eventually, this leads to the breakdown of a layer of the retina called the retina pigment epithelium and the disruption of blood vessels directly behind the retina. When this occurs, nutrients from the blood are unable to reach the eye due to the degradation of the blood vessels and the retinal membrane. The lack of nutrients in the eye ultimately causes light-sensing photoreceptor cells in the eye to die, leading to blindness.
Figure 1: In age-related macular degeneration, nutrients are unable to travel from the choroidal blood vessels to the photoreceptors, causing the death of photoreceptors and blindness.
SUN ET AL., JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2021), DOI: 10.1111/JCMM.16882
Alternatively, in wet age-related macular degeneration, the blood vessels directly behind the retina start growing too rapidly. This overgrowth in blood vessels can penetrate the retina pigment epithelium and leak blood directly into the eye. The leakage of blood into the eye separates the eye’s crucial light-sensing photoreceptor cells from the retinal membrane and prevents the cells from receiving nutrients through the retinal membrane. Due to a lack of nutrients, the photoreceptor cells die, leading to blindness.
One of the biggest questions facing the researchers was to investigate the role that a specific protein plays in macular degeneration. Vascular endothelial growth factor (VEGF) is responsible for promoting the growth of blood vessels behind the retina. Due to its crucial role in blood vessel growth, an increase in VEGF secretion has been linked to wet age-related macular degeneration. However, it is unclear what molecular changes in the retina occur that initiate a higher secretion of VEGF.
With this, Song et al. were interested in creating an accurate 3D model of the eye’s retina and blood vessels that could emulate both dry and wet age-related macular degeneration. This would allow the researchers to investigate molecular changes in the eye responsible for initiating increased VEGF production and the progression of wet and dry age-related macular degeneration.