Many eye diseases, such as Retinitis Pigmentosa, Leber Congenital Amaurosis (LCA) and Stargardt Disease, have a genetic basis. Researchers are studying these and other inherited retinal diseases in order to identify the genes responsible and to use this information to develop genetic tests and treatments. Research projects at the National Eye Institute, Oregon State University College of Pharmacy, and Oregon Health & Science University have identified certain genes responsible for inherited retinal diseases and have found a way to deliver nanoparticles to the retina.
Genetic Discoveries in Retinal Dystrophy
Researchers at the National Eye Institute, part of the National Institutes of Health have identified a gene responsible for some inherited retinal diseases. These diseases are rare, which makes it difficult to find enough participants for studies and clinical trials.
Researchers studied six unrelated individuals and were able to link the gene UBAP1L to different types of retinal dystrophies. These dystrophies affect the macula—the part of the eye used for reading—as well as the cone cells that enable color vision and rod cells that enable night vision. The subjects’ symptoms of retinal dystrophy started in early adulthood and eventually lead to severe vision loss by late adulthood.
Further genetic evaluation of these persons uncovered four variants of the UBAP1L gene. These variants encode for a protein that is expressed in the retina cells, including the retinal pigment epithelium and photoreceptors. Researchers found that the variants caused the gene to produce protein that lacks function. Another important finding from this study was that five out of the six families were from South or Southeastern Asia and Polynesia, areas that have been underrepresented in genetic studies.
“These findings highlight the importance of providing genetic testing to our patients with retinal dystrophy, and the value of the clinic and lab working together to better understand retinal diseases,” said co-senior author on the paper, Laryssa A. Huryn, M.D., an ophthalmologist at the National Eye Institute.
Nanoparticles to the Rescue
Scientists at the Oregon State University College of Pharmacy and Oregon Health & Science University have developed a new type of lipid nanoparticle that is capable of reaching the eyes. This can be used for inherited eye diseases.
This lipid nanoparticle is able to reach the retina and deliver the medicine. It is based on the compound thiophene, and researchers call these lipids Thio-lipids. This study demonstrated, through the use of animal models, that the Thio-lipids in the lipid nanoparticles can be used to deliver messenger RNA (mRNA) or CRISPR-Cas9 gene editors to treat genetic blindness. For example, the mRNA in the Thio-lipids would tell the cells in the retina to manufacture the necessary proteins for sight.
The current method of delivery for gene editing, adeno-associated virus (AAV) has its limits. AAV has inadequate packing capacity, its use can lead to an immune response, and it doesn’t always perform effectively when it comes to DNA editing. So, the Thio-lipids could be a viable alternate. Of course, more research is needed.
As researchers push the boundaries of genetic medicine and develop innovative treatment strategies, there is reason for optimism when it comes to inherited retinal diseases. The progress made in identifying genetic causes of retinal diseases and developing new delivery methods, like Thio-lipids, underscores the exciting potential for future breakthroughs in treating blindness. Although challenges remain, these cutting-edge approaches bring us closer to viable therapies that could one day restore sight for countless individuals facing genetic vision loss.