‘Fibroblast Reprogramming’ for Macular Degeneration

The research for every possible application to slow or eradicate macular degeneration continues. From pharmacological and invasive injection therapy to medical marijuana and acupuncture, much good data is getting researchers closer to stopping this disease. This includes the incredible advancement of stem cell science which is capable of reprogramming human cells to takeover where compromised cells are malfunctioning. 

Now, new research shows the unique application of skin fibroblast cells, an alternative to stem cells, being used to replace damaged photoreceptor cells. This is known as ‘fibroblast reprogramming’ a specialized process that may take the lead in AMD prevention and treatment. 

Fibroblast reprogramming for macular degeneration brings new hope for yet another useful weapon in the fight against this devastating ocular disease.   

Stem Cells Good, Fibroblast Better

Science continues to forge ahead with highly successful testing and some treatments using stem cells to slow or stop macular degeneration progression. In several animal lab models the application of stem cells has shown great promise in stopping AMD. Stem cells are described as blank slates able to be coded with any human application to generate healthy cells. 

According to the Mayo Clinic, 

“Stem cells are the body’s raw materials — cells from which all other cells with specialized functions are generated. Under the right conditions in the body or a laboratory, stem cells divide to form more cells called daughter cells. These daughter cells either become new stem cells (self-renewal) or become specialized cells (differentiation) with a more specific function, such as blood cells, brain cells, heart muscle cells or bone cells. No other cell in the body has the natural ability to generate new cell types.”

However, stem cells are difficult to cultivate. Fibroblasts, which are cells found in connective tissue which produces collagen and other fibers, may be more viable.

Sai Chavala, Ph.D. and author of the new paper on fibroblast research comments that generating stem cells requires complex and time-consuming work. Fibroblast cells can be manipulated chemically and the results have been significant. 

GNN reported on this research stating that,

“Fibroblasts are cells that help maintain the structural integrity of connective tissues, and a reduction in fibroblast cell count leads to wrinkled skin. Dr. Chavala and colleagues from the Center for Retina Innovation in Dallas, Texas, found a set of five compounds that can drive embryonic fibroblast cells to convert themselves into retinal, rod-like, photoreceptors in both mice and human cells.”

Photoreceptor Fix

One of the most important set of neurons in the eyes are the photoreceptor cells. They are responsible for switching on the visual circuitry when exposed to any level of light enabling you to see. Macular degeneration can attack these cells, compromising the ability to function properly and eventually causing irreversible blindness. 

Stem cells have not been able to regenerate quickly enough to enable a way to scale a viable treatment for mass application. However, in laboratory testing, chemically activated skin fibroblast cells presented as regenerating damaged photoreceptor cells more rapidly. This testing was described by Dr. Chavala as a “breakthrough” due to the ability to convert these cells in “a fraction of the time” when transplanted into the eyes of 14 blind mice. 

According to the paper, ‘Pharmacologic fibroblast reprogramming into photoreceptors restores vision’ by Dr. Chavala and a team of researchers which was published in Nature (415/20),

“Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision. Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss…Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the sub-retinal space of rod degeneration mice leads to partial restoration of the pupil reflex and visual function…We anticipate that CiPCs could have therapeutic potential for restoring vision.”

The DNA damage experienced by photoreceptors is described as similar to scratches on compact disc. These scratches and cracks prevent laser reading of information on the disc. In the body the laser is the RNA and the CD is the DNA. When this damage occurs the DNA cannot be repaired and blindness ensues. With fibroblast applications there is a chance that, due to the speed of regeneration, the damaged DNA can be reversed and restored. 

A Hopeful Sign

As the laboratory mice showed signs of successful vision, the beneficial results continued. Over the next few months the mice were monitored for progression or regression. 

Lifespan reported that, 

“To determine whether the transplanted photoreceptors continued to function and had connected to deeper neural cells, the researches followed up on the mice three months after the transplantation. They found that the mice that had exhibited improved visual function retained it. Moreover, CiPCs were found to develop synaptic terminals that apparently transmit light signals into the inner retinal neurons.”

This transference of ‘synaptic terminals’ means that the brain could be adapting naturally to the transplantation. This has lead to more testing as fibroblast reprogramming is being tested on humans and is showing similar results. Dr. Chavala remains hopeful for this therapy for not only macular degeneration but future health applications stating,

“We believe this can be a game changer in the field of regenerative ophthalmology. We also believe this is a platform technology and have already started establishing protocols to generate retinal ganglion cells valuable for patients suffering from glaucoma,”

You may hear more about fibroblast reprogramming for macular degeneration and possibly many other health applications as well. It is a tribute to the continued and tireless research that keeps the lights on while the lights are slowly going out.