Numerous vision diseases, such as glaucoma, retinitis pigmentosa, and, to a certain degree, diabetic retinopathy, have a genetic basis. Wouldn’t it be great to learn about the genetic makeup of these and other vision diseases so that treatments can start earlier, when they are most effective? Two research projects are studying both what is going on at the genetic level and how nanoparticles can deliver material at the genetic level to treat inherited diseases.
Meta-Analysis of Glaucoma
Researchers from the Massachusetts Eye and Ear conducted a study that combined a meta-analysis of studies on primary open angle glaucoma with a meta-analysis of studies on intra-ocular pressure. These analyses revealed cell types, specific genes and biological processes that affect the development of primary open angle glaucoma, both related to intra-ocular pressure and independent of intra-ocular pressure.
Scientists identified hundreds of genes that contribute to glaucoma risk. They also looked at data from other tissues and were able to identify both known and lesser-known cell types where gene dysregulation may affect optic nerve degeneration. The pathways identified in this analysis can impact different structures in the eye and how they interact with different genes and cell types that may lead to primary open angle glaucoma. These findings provided new insights about gene expression and post-transcription gene regulation, both of which could lead to improved drug design for glaucoma. Furthermore, this research indicates that targeting the neuronal support cells, as well as the retinal ganglion cells, should be a considered when developing new drugs and therapies.
Genetic Treatments for Hereditary Vision Loss
The research at Massachusetts Eye and Ear showed that certain cells could be used as targets for treatment. The next question is: What kind of treatments?
As you can guess, scientists are also working on the answer to that question. Researchers at the University of Oregon College of Pharmacy and the Oregon Health & Science University have developed lipid nanoparticles that are able to travel to the retina and deliver the necessary therapy. They call these nanoparticles Thio-lipids since they are based on the compound thiophene.
Using mouse models, the study showed how it could be possible to use the Thio-lipids to deliver messenger RNA to treat genetic blindness. The lipids in the nanoparticles wrap around the messenger RNA and CRISPR-Cas9 gene editors that are used to treat genetic diseases. The chemical structure of the lipids determines the potency of the nanoparticle and which organ they can reach via the bloodstream.
For example, if this is used as a therapy for inherited retinal degeneration, the messenger RNA would tell the cells in the retina, which don’t work properly as a result of a genetic mutation, to make the proteins needed for vision. The current means of gene editing utilizes a kind of virus known as adeno-associated virus and the study’s purpose was to address the limitation of delivery via the virus.
The virus’ limitations include limited packaging capacity and it can prompt an immune system response. It also doesn’t do well in creating the enzymes the editing tool uses as scissors to make the needed cuts in the DNA. So, the study of Thio-lipid serves as a proof of concept. Of course, more studies will be needed, including research on the long-term impact of the lipids on retinal health.
These research projects at Massachusetts Eye and Ear and the University of Oregon College of Pharmacy and the Oregon Health & Science University are more examples of how medical research is expanding our understanding of the genetic makeup of vision diseases, like glaucoma or retinitis pigmentosa. Learning the genetic makeup of these and other vision diseases can show what is going wrong at the genetic level and the Thio-lipid nanoparticles can be utilized to fix what is broken. The research about the nanoparticles and the meta-analyses demonstrates that fixing the faulty DNA sections to improve the eyesight of persons with vision diseases, isn’t just conjecture. It works in mouse models and it can be utilized in humans.