Our vision is one of the most important senses that we use in our everyday lives. Whether its to help somebody perform complex surgeries or soak in a beautiful impressionist painting, a layer of cells in the back of the eye called the retinal pigment epithelium (RPE) provide support to photoreceptors (PRs), specialized cells that play an important role in our ability to process images. Unfortunately, as we get older, problems with this part of the eye can begin to develop.
Age-related macular degeneration (AMD) is an eye disease that causes severe vision impairment, resulting in the inability to read, drive, recognize faces, and blindness if left untreated. It is the leading cause of vision loss in the U.S. and currently affects over 2 million Americans. By the year 2050, it is projected that the number of affected individuals will more than double to over 5 million. The dysfunction and/or loss of RPE cells plays a critical role in the loss of PRs and hence the vision problems observed in AMD. One form of AMD for which there is no treatment is known as dry AMD (dAMD) and accounts for about 90% of all AMD cases. This version of dAMD is due to the inability of the RPE cells to heal.
CIRM-funded research at UC Santa Barbara aims to create a platform to test therapies for dAMD. Led by Dr. Peter Coffey and Dr. Lindsay Bailey-Steinitz, the team outlined two main objectives for this project. The first was to better understand what is occurring at the cellular level as the disease advances. The second was to develop a model that could be used to test therapeutics.
In a press release, Dr. Bailey-Steinitz discusses the importance of developing a disease model for dAMD.
“Part of the struggle of finding a treatment option is that we’ve not been able to really model the progression of the disease in cell culture or in animals.”
In dAMD, when RPE cells fail to repair themselves, they form a hole that gradually continues to expand. Dr. Bailey-Steinitz recreated this hole in the lab by culturing RPE cells on a plate with an electrode and then zapping them. This process created a hole very similar to the one that appears in dAMD. However, since the cells used in this experiment were younger cells, they were more prone to self healing. But the team found that 10 pulses of electricity over the course of 10 days prevented the younger cells from healing. The team also found that shocking the cells suppressed important genes involved in RPE cell function.
The team is planning future experiments with older cells since they demonstrate a decreased ability to heal.
In the same press release, Dr. Coffey highlights the potential impact of this work.
“”If we can improve this setup, then we’ve got a therapeutic testbed for AMD.”
CIRM has also funded a separate clinical trial for dAMD conducted by Dr. Mark Humayun at the University of Southern California.
The full results of this study were published in PLOS ONE.
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All cells require growth factors for growth, differentiation, behavior and functional. In resting cells, they require growth factors to maintain their surviving. The interaction of growth factors to receptors on the surface of cell activaties intracellular signaling which may induce genes expression for functioning of cell. In the elderly people, the lack of growth factors produce in body cause many kinds of diseases related with olden age. Therefore, Age-related Muscular Degeneration (AMD) is commonly happened in elderly which cause most of the elders loss their vision or turn blindness. The report showed that 90% of AMD cases were dry-AMD, which was due to inability of RPE cells to heal. All living organisms require growth factors and hormones to regulate growth before attaining maturation. However, most of the endocrine and reproductive organs cease operation during olden age. The supplement of growth factors and hormones provide additional advantage for supporting RPE cells to survival and grow. The lack of growth factors and hormones suppresses majority of genes (LRAT, MITE, RDHLL) associated with RPE to become downregulated. This will eventually causes RPE cells fail to repair themselves and form a hole which can gradually expand to deteriorate the vision from elderly.
Stem cells therapy is another alternative approach to repair the loss of RPE cells in eye. The supplement of growth factors may significantly improve the vision of AMD patients.
The electrical pulse of culturing RPE cells in several times may cause permanently paralyse the system of signaling network and cease the RPE related genes from expression.