I Can See Clearly Now the GABA is Almost Gone! - How Zebrafish Recover From Blindness

A recent study funded by the National Eye Institute found a link between the neurotransmitter GABA, or gamma-aminobutyric acid, and recovery from blindness in zebrafish.  For some time now, scientists were aware of the zebrafish's ability to recover from loss of vision that would normally blind humans permanently.  This is due to the zebrafish having a miraculous ability to regenerate cells in the retina.  Prior studies showed that dying retinal cells produced signals to trigger Muller glia, which revert back to an undifferentiated state and divide.into new cells.  Studies in mice on the brain and pancreas indicated that GABA could play a role in the regeneration process, where low levels signaled stem cells to  divide.  The researchers of the current study, therefore, hypothesized that GABA in zebrafish could be a factor in the regeneration of retinal cells.  To test their theory they injected zebrafish with GABA inhibitors.  They found that these fish responded with retinal cell regeneration.  Fish with retinal damage that were given high levels of GABA, on the other hand, displayed little to no regeneration.  These findings clearly support the hypothesis that GABA plays a very important roll in the regeneration of new cells.

I found this article interesting because I often joke about how I'm going blind because my vision is so poor.  But on a serious note I think the findings in this study could be very significant for finding cures to diseases in humans that affect vision, and it could lead to new treatments to cure blindness.  It is also the first study to report these kind of results, so with more experiments in the future it would be fascinating to see what else researchers find out about the subject.

How fish can regenerate eye injuries at the cellular level

Fish have the special ability to regenerate injuries to the retina at a cellular level. Scientists from Heidelberg University’s Centre for Organismal Studies, or COS, have discovered as to how the regeneration process starts by studying the Medaka fish. There is one genetic factor that triggers two steps for this process to occur. The two steps are cell division and differentiation of progenitors into new and different cell types. Stem cells have been a huge topic as of late in the medical world. Stem cells can be used to correct faults in the body. However, we have not yet been able to actually figure out how to perfect this system. One-day scientists hope that we will actually be able to use stem cells to help repair various injuries. In a study, researchers looked into the retina of fish and found that they can completely repair injuries to the retinal nerve cells. There are special glia cells that act like stem cells. Both fish and humans have these cells in their eyes. These cells are also called Muller cells. Professor Wittbrodt of COS explored if these cells could be activated and what would stimulate the regeneration process. A gene called Atoh7 is responsible for cell differentiation and is triggered by a single genetic factor. There are several steps that go into the regeneration process of a fish’s eye. The glia cells first start to proliferate. “First the Müller cells near the injury start to proliferate. The resultant neuronal clusters contain the progenitor cells for the cell types of the retina. In the last step, these progenitors differentiate and turn into the neuronal retinal cells to be restored”. These cells supposedly show signs of being able to repair any injuries. The Atoh7 gene is the big factor, which fulfills two functions and triggers proliferation and differentiation into various retinal cell types. Scientists hope that one day we will be able to decode this ability in humans.

Regeneration is a very interesting and unique ability that various species possess. By studying these species more and more I believe that one day we will be able to figure out a way to possess this ability in humans. Being able to cure someone’s blindness would be a miracle. Hopefully one day it will only take one simple surgery for someone to repair their damaged retinal cells. I think more research and funding should go into fully understanding the regeneration process.

Links:

https://www.sciencedaily.com/releases/2016/05/160506100241.htm

http://www.eurostemcell.org/factsheet/regeneration-what-does-it-mean-and-how-does-it-work

Gene Therapy Could Cure Congenital Eye Blindness

Recently scientists at the University of Oxford have developed a gene therapy treatment in the hopes of reversing the affects of congenital eye blindness. Congenital eye blindness is a genetic disease that effects 1 in every 50,000 people, most commonly  males. The disease is due to a single gene mutation that causes a gradual loss of light detecting retinal cells. Patients are born with full eye sight and find that their vision progressively narrows until they eventually become completely blind. As of yet there have been no successful treatments developed to slow the progression of this disease. However, there have been many attempts to develop treatment for a number of eye conditions. Diseases effecting the eye are often caused by only one or two genes and eyes can be easily accessed for administration of treatments, this makes eye conditions desirable for scientists to work on. 

The gene therapy treatment developed by the scientists at the University of Oxford is administered through an injection into the eye. The injection contains a virus administered directly into the retina. This virus contains billions of functioning copies of the defective gene. With this working copy the retinal cells can in turn function properly. This experimental treatment was administered to six patients. In wonderful news results from the study published in the New England Journal of Medicine on April 28, 2016 reported that the treatment had seen great success. After four years not only did the treatment slow progression of the disease, it reversed the effects in some cases. The youngest tested patient received the best results, leading scientists to the conclusion that early administration is best. However, all patients regardless of age saw astounding results. The success of this treatment has scientists hopeful in the successful treatment of other eye conditions. I am interested to see where this great success takes the treatments of genetic eye diseases, and how the study of this therapy on a larger population size results. 

'Miracle' Gene Therapy To Cure Blindness

Dr. Jean Bennett, a gene therapist at the University of Pennsylvania, and her colleagues, began treating people who are blind with injections of a harmless virus that inserts good copies of genes that are defective in the patient. The genes were inserted into the cells of the retina. The retina is a light sensitive tissue at the back of the inner eyeball. Its job is to receive light and convert that light into neural signals to which the brain uses for visual recognition.

In 2007, researchers began conducting gene therapy clinical trials on ten patients with Leber’s congenital amaurosis Type 2. Leber’s congenital amaurosis Type 2 causes a degeneration of retinas thus limiting vision at birth and progressive blindness by mid life. The ten patients, ages ranging from 20-45, underwent gene therapy only in one of their eyes, the one which had the worst vision. After gene therapy for two or three years, researchers used an MRI to scan deep into the patients’ brains. The MRI showed the visual pathways in each patient was nearly as strong and healthy as a normal persons vision at that age. The MRI scan also showed the untreated eyes had much weaker visual pathways. This observation suggested that regaining sight also helped to rebuild the visual pathways in the brain. This revision is called brain plasticity.

The data collected from this study hinted that the patients’ visual pathways were in better condition after more and more time had elapsed since undergoing gene therapy. Because the pathways improve as more signals get sent through, Bennett and her colleagues are working on larger phase trials to determine whether their gene therapy can be used more widely as treatment.

This article and the research behind it were truly remarkable. The patients undergoing gene therapy are in their 20’s, and one patient was 45. This age range demonstrated visual pathways and brain plasticity could be improved at any age, not just young children. I found this article to be extremely uplifting and encouraging in the field of gene therapy. The ability to use gene therapy in repairing a person’s sight that had been nearly blind is just so moving.

Cure for a Rare Form of Color Blindness Steps Closer with Gene Insight

Researchers have uncovered insights into two genetic mutations that may be a cause of a rare form of color blindness called achromatopsia, and is paving the way for a cure. Achromatopsia is a rare, inherited disorder that affects 1 in 33000 people in the US. This condition is triggered by abnormalities in the retina - a layer of tissue at the back of the eye containing cells that are sensitive to light. People with this disorder will experience partial or total loss of color vision, as well as sensitivity to light, As of right now, there is no cure for achromatopsia, but the use of red - colored lenses reduces the sensitivity to light and also boosts visual functioning. 

Karina Guziewicz, of the School of Veterinary Medicine at the University of Pennsylvania, and colleagues began their study by analyzing the vision of a German Shepherd dog whose owners were concerned about its vision. The team analyzed five genetic mutations that were known to play a part in how light signals are sent from the eye to the brain, a process called phototransduction. As a result, the team identified a mutation in a gene called CNGA3 that was responsible for the dog's vision loss. The team analyzed dogs that had similar symptoms to the German Shepherd, and found a different mutation on the same area of the CNGA3 gene. The team notes that the mutation found in the German Shepherd has been found in humans, so dogs can be a valuable model to study achromatopsia. 

I thought this article was very interesting, I would never have thought to study dogs for this disease. I hope this team, or the many other scientists out there, finds a cure for this disease  as it is harmful. A person with this disease will be sensitive to light, and a absence of color vision. I hope a cure is made in the future to combat this disease.

Link for the article here 

Embryonic Stem Cell Therapy Reports of Long-Term Safety to Treat Human Disease

The Lancet recently published new research in which the first evidence of "medium-term to long-term safety and tolerability of transplanting human embryonic stem cells (hESCs) in humans has been revealed by scientists." The study was conducted on 18 patients who had severe vision loss. They received hESCs and appear to be safe 3 years post-transplant. More than half of the patients experienced restoration of some sight.

"Embryonic stem cells have the potential to become any cell type in the body, but transplantation has been complicated by problems including the risk of teratoma formation and immune rejection," Professor Robert Lanza, Chief Scientific officer at Advanced Cell Technology in the USA. "As a result, immunoprivileged sites (that do not produce a strong immune response) such as the eye have become the first parts of the human body to benefit from this technology."

The participants had one of two different types of eye disorders, half having Stargardt's macular dystrophy and the other half having dry atrophic age-related macular degeneration. Both of these conditions have no effective treatment and they can both lead to complete blindness. The hESCs were differentiated into retinal pigment epithelium cells and were injected in different doses. Some patients received 50,000 retinal cells, some 100,000, and some 150,000 cells. These cells were placed into the space under the retina of the eye (the area with the worse vision).

The hESC cells were accepted and tolerated for "up to 37 months after transplantation." If the patients experienced any adverse effects, after close analysis, it is safe to say that they were not caused by the hESCs. Additionally, 10 of the 18 patients claim to have had significant improvement in their vision in the eyes that received the stem cell treatment.

"Our results suggest the safety and promise of hESCs to alter progressive vision loss in people with degenerative diseases and mark an exciting step towards using [these] stem cells as a safe source of cells for the treatment of various medical disorders requiring tissue repair or replacement," co-lead author Dr. Steven Schwartz, Jules Stein Eye Institute.

Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, states how this study is a "major accomplishment" but also that "much work remains to be done before hESC and induced pluripotent stem cell therapies go beyond regulatory trials, but the path is now set in motion."

I absolutely loved this article because I have always had great interest in stem cell therapy. This is a huge step forward for the practice and potential use of hESCs as common treatments for certain disorders or anything else requiring the repair or replacement of tissues. I'm very excited for what is upcoming in the medical field because of advancements such as this in the area of stem cell research and therapy.

Article: http://www.sciencedaily.com/releases/2014/10/141014211709.htm 
Related Article: http://health.usnews.com/health-news/articles/2014/10/14/embryonic-stem-cell-therapy-shows-long-term-effectiveness-safety 

Bad Eyes? Gene Found to Affects Retinal Degeneration

Have you ever wondered why eyesight, mainly retina, worsens as you grow? Scientists, from Georgetown University of Medicine, have found that the hormone Klotho can lead to macular degeneration. Scientists have found that the hormone Klotho could increase synthesis of light absorbing pigments, increase of gene expression that protect against oxidative stress, inhibition of vascular endothelial growth, and is found to regulate phagocytosis in the photoreceptors. 

This correlation enables scientist to be able to manipulate this hormone to reduce macular degeneration.
Also, I think this can come handy to even just understand the relationships between hormones and their effects on cells.


http://www.medicalnewstoday.com/releases/267179.php

http://www.uniprot.org/uniprot/Q9UEF7