However, all surgeries have possible side effects, including the formation of scars. Scarring in the eye can be particularly damaging to vision. Unfortunately, aniridia patients are particularly prone to severe post-surgical scarring after eye surgeries (aniridia fibrosis syndrome (AFS)) one, which is so severe that it can itself cause blindness. Currently, this is treated by surgically removing the scar tissue, but more surgery may also contribute to severe complications and more scarring. We propose that AFS arises in aniridia patients because Pax6 is important for eye cells to remember that they are eye cells over the lifespan, and that when Pax6 levels are decreased (as in aniridia), cells that should be eye cells instead convert to the cells that make scar tissue. We have some preliminary evidence that this occurs in AFS.
Notably, we also have evidence suggesting what Pax6 does to prevent the formation of scar tissue in normal eyes (blocks Wnt and TGFbeta signals which drive scar tissue formation), and have shown that this does not occur in aniridic eyes. Further, we have mice which also develop aniridia due to loss of a copy of the Pax6 gene and have shown that they are also very prone to post-surgical scarring. We propose to first prove the connection between aniridia and increased scar tissue formation in these mice. Next, we propose to follow up on our prior work that suggests that Pax6 prevents uncontrolled scarring in normal eyes by shutting off two important mechanisms driving scar tissue formation, transforming growth factor beta and Wnt signaling. If we can prove this connection, we will then use the animal model to test possible ways to prevent and/or treat AFS using known drugs that turn down scar tissue by blocking the function of the identified causes. The overall goal of this work is to determine how AFS occurs then to use this knowledge to identify drugs (initially ones under development or in the clinic to block other types of scarring) to prevent and/or treat AFS, helping aniridia patients maintain their vision throughout their lives.
Learn how to participate in the AFI Medical Registry which assists the medical and research community.
Aniridia Foundation International’s (AFI) Medical Registry is an important aspect of vision research. Because aniridia syndrome is made up of multiple eye and medical issues, this data collected for research will help those with aniridia AND potentially those that experience the common ophthalmic and medical conditions found in aniridia syndrome such as: glaucoma, cataracts, corneal scarring, ophthalmic fibrosis issues, diabetes / glucose intolerance, obesity and autism spectrum disorders.
The adults, children or families with multiple aniridic family members that participate in our research data collection are dedicated to being part of the “solution” and working towards better treatments, advancing research knowledge and eventually a cure for themselves and the children of today and tomorrow. If you would like to participate, please contact our office. There are multiple ways to participate and you can do as much or as little as you wish.
Contact us. Please provide your name, phone and the person(s) with aniridia so that we may contact you with how you can Help Us Make a Miracle! You do not have to be a member of AFI to participate, however, AFI membership does provide many benefits to you and your family. Become active in AFI and register as a member. It’s FREE.
Aniridia Fibrosis Syndrome (AFS) Research
Melinda K. Duncan, Ph.D.
AFI Scientific Board Member
Professor, Graduate Program Director
Department of Biological Sciences
University of Delaware
James D. Lauderdale, PhD
Chair, AFI Scientific Board
Assistant Professor in Cellular Biology
Department of Genetics
University of Georgia - Athens
What thoughts come to mind when you hear the word “bio-engineering?” For a team of researchers led by Dr. James D. Lauderdale (Department of Cellular Biology and Neuroscience Division of the Biomedical Health Sciences Institute, University of Georgia) and Dr. Phillip Anthony Moore (College of Veterinary Medicine, Auburn University), it means developing the potential to restore sight for people who have suffered catastrophic vision loss. Drs. Lauderdale and Moore are engineering replacement tissue that can be used to treat diseases or injury that affect the front of the eye, particularly the cornea.
The cornea is the transparent front part of the eye that covers the iris and pupil, and it serves two important roles. First, it focuses the entry of light into the eye and contributes between 65-75 percent of the eye’s total focusing power. Second, the cornea helps to shield the rest of the eye from germs, dust, and other harmful matter. A special group of cells at the edge of the cornea, called limbal stem cells, are needed to keep the cornea healthy and in good working order.
Injury such as corneal infections, chemical and thermal burns, radiation injury, and genetic diseases can cause loss of vision. Because these injuries damage limbal stem cells, traditional eye surgery such as corneal replacement is ineffective at restoring vision in these cases. Using state of the art technology, Drs. Lauderdale and Moore are engineering corneal tissue that can be used to replace the damaged limbal stem cells and restore vision in people with these disorders.
Aniridia-related keratopathy (ARK) is estimated to occur in 90% of aniridic patients and is an important factor contributing to the progressive loss of vision in these individuals. Although aniridic children start life with clear normal-looking corneas, their corneas begin to degrade as they age. The pathogenesis of ARK is potentially due to a congenital corneal limbal stem cell deficiency (LSCD), a diseased state characterized by impaired corneal wound healing and loss of corneal integrity.
Drs. Lauderdale and Moore are in the process of developing a cell-based approach capable of preserving a clear cornea for the aniridic child through adulthood. To accomplish this goal, they propose to remove some of the aniridic patients’ cells from the limbal region, culture those cells to make more, introduce a copy of the PAX6 gene into the patient’s own cells, and then transplant those cells carrying the extra PAX6 gene back into the patient’s eyes. They have successfully demonstrated this technique using rabbits and are in the process of developing the protocols necessary for extending this work to people. Additionally, Dr. Lauderdale’s research group is currently developing approaches that permit direct correction of certain types of PAX6 mutations that can be used in conjunction with these and other cell-based approaches for managing ARK. For Drs. Lauderdale and Moore, the future is in sight.
Aniridia Foundation International's Medical and Scientific Boards collaborate with researchers worldwide to assist and conduct life changing research. Our research program, The AFI Medical Registry, is one of the most important components of these collaborations because it houses crucial data that allow researchers to study a large population. This data was not available just a decade ago when Aniridia Foundation International was first founded.
Aniridia syndrome is just one of many congenital eye disorders usually found at birth. Since it is a "syndrome" it is defined by multiple ophthalmic and medical conditions, of which some conditions are often found commonly in the general population. For this reason, research is important because what we learn about glaucoma for example, will assist with research and education advancement for all people with glaucoma, not only those with aniridia.
We appreciate the work of these partnering researchers who work to better the lives of those with aniridia syndrome and investigate the conditions which make up this genetic congenital eye disorder.
Please help AFI support these important research initiatives. Donate to AFI and indicate “Research” on your check (made payable to Aniridia Foundation International.) Or use our AFI online donation form.
Congenital aniridia is a condition diagnosed when a baby is found to lack the iris (which controls the amount of light coming into the eye) at birth. In most cases, these babies have a damaged or absent copy of the Pax6 gene, so that these babies make less Pax6 than normal. The right amount of Pax6 is necessary to tell the appropriate cells of the embryo to make an iris, and too little Pax6 means that not enough of this instruction is being made. However, the correct amount of Pax6 is also important to make other structures of the eye, and to keep them healthy once they are made. Thus, as aniridia patients age, they will be affected with other eye diseases, such as glaucoma, cataract, and corneal cloudiness (scarring), which require surgical treatment if the person is going to be able to retain their vision.