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Cutting the Fat & Turning Back the Clock

Posted by Ilena Di Toro | Posted on February 2, 2021

During the coronavirus lockdown, many people used this time to exercise more. As a result, their clothes aren’t as tight and they felt better. The bad thing about the lockdown is that it led to a lot of shortages, like toilet paper. Too bad we can’t turn back the clock to February 2020 and stock up on toilet paper.

Researchers were able to find ways to cut out genetic material and even turn cellular clock back in order to prevent vision loss.

Let’s begin with cutting the genetic material. Researchers at Louisiana State University (LSU) Health Sciences Center New Orleans were able to delete one of the inhibitors of the RPE65 gene in a mouse model. This inhibitor is responsible for degeneration of the cone photoreceptors that are used for daytime color vision. The mutation of the RPE65 gene can lead to retinal diseases such as Leber congenital amaurosis (LCA). While there is gene therapy that can improve vision for some people with the RPE65 gene mutation, there isn’t a way to stop the degeneration.

Researchers found that a protein, known as the fatty acid transport protein 4 (FATP4) that is an inhibitor of RPE65. When FATP4 wasn’t in the retina of the mouse model, the survival of the cone photoreceptors increased almost 10-fold. In addition, partial reduction of the FATP4 improves the survival and function of the cone photoreceptors. This shows that FATP4 can be used as a therapeutic target to keep daytime color vision those with LCA.

“This study is the first to uncover that FATP4 plays a pivotal role in photoreceptor survival and function in retinal dystrophies,” says Nicolas Bazan, MD, PhD, Boyd Professor, Ernest and Yvette C. Villere Endowed Chair for Retinal Degenerative Diseases and Director of the Neuroscience Center of Excellence at LSU Health New Orleans School of Medicine.

What about turning back the clock? Is there a way to reprogram genetic material, so that vision isn’t lost in first place? That’s what researchers in Harvard did. They restored vision in mice by reprograming complex tissue back to its youthful functionality.

Scientists at the Blavatnik Institute at Harvard Medical School used an adeno-associated virus (AAV) to deliver into the retinas of mice three genes Oct4, Sox2 and Klf4. These genes had many positive effects on the eye. It promoted nerve regeneration after optic-nerve injury. It reversed vision loss in animals with a condition that mimicked human glaucoma. It also reversed vision loss in aging animals without glaucoma.

This research is based on a new theory about why we age. Most cells in the body contain the same DNA molecules but have diverse functions. To do their specific function, the cells have to read only the gene specific to that function. The cell’s epigenome, a system of a system of turning genes on and off in specific patterns, regulates the cell’s work. Over time the epigenome causes the cell to read the wrong genes and this leads to diseases of aging, such as glaucoma.

One big change to the epigenome is DNA methylation, a process by which methyl groups are tacked onto DNA. Over time the patterns of methylation get lost and the genes can’t do their job the way they were designed to do it. Yet some of the DNA methylation changes are predictable. Researchers thought that if the DNA methylation controls aging, getting rid of some of its “footprints” would reverse the effects of aging in the cell and return it to a more youthful state.

Oct4, Sox2 and Klf4 were used in a mouse model of glaucoma and the treatment increased both the nerve cell electrical activity and visual acuity. What’s great about this is that the improvement in the mouse model vision happened after vision loss occurred. That’s not all. When researchers looked at the molecular changes in the cell, they found reversed patterns of DNA methylation. That means the DNA methylation isn’t just a marker of the aging process, it is causing it to happen. If the findings are confirmed in further animal work, researchers could start clinical trials within two years to test this method in people with glaucoma.

So, trimming the fat is good both for our waistlines and at the cellular level. Now if we could only figure out a way to turn back the clock to January 2020 and invest in Zoom stock.


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