We here at Eyehealthweb like to think that we’re making some small difference in the lives of our readers by providing you with easy to understand, medically accurate information about eye health. But there are others who are doing much more.
Numerous non-profit organizations exist whose members work tirelessly to improve others’ vision or to help people to cope with vision loss. Some of them are large, well-known institutions with full-time staff numbering in the hundreds; others are small, grassroots organizations operating out of individuals’ homes. All of them deserve support and recognition from the public at large, and with this in mind we present here an in-depth profile of three of these groups—The Foundation Fighting Blindness, The Choroideremia Research Foundation, and The Cornea Research Foundation of America.
The Foundation Fighting Blindness
The Foundation Fighting Blindness began as the Retinitis Pigmentosa Foundation, which was founded in September 1971 by Gordon Gund and Bernard “Ben” Berman, along with about a dozen other founding members, including Berman’s wife, Beverly. Its purpose was to support research that might lead to a cure for this degenerative eye disease, with which Berman’s two daughters, Mindy and Joanne, had just been diagnosed. Gund too suffered from retinitis pigmentosa, and had lost his vision to it the year before.
The Foundation eventually broadened its focus to retinal disorders of all kinds, and even interested itself in other sight-threatening conditions, including genetic disorders such as Usher Syndrome. In 1995 it was renamed The Foundation Fighting Blindness (FFB). During the course of its more than forty years of existence, the Foundation has funded thousands of research studies at prominent institutions all over the world, including Harvard, the Peking University Medical Center, and the University of Iowa.
Much of the Foundation’s support comes from donations. Eyehealthweb recently spoke with FFB’s chief research officer, Dr. Stephen Rose, and Ben Shaberman, its senior science writer, who were kind enough to take the time for a brief telephone interview. They told us about FFB’s various fundraising events, including Dining in the Dark, a dinner event at which the lights are turned out before the entrée is served so that guests can experience, briefly, what it’s like to have to function without sight. Meals are served by visually impaired waitstaff, and the diners eat in complete darkness for thirty minutes. This event is held regularly in cities across the United States, and may very well be coming to your city soon (check FFB’s web site for details).
Dr. Rose and Mr. Shaberman also provided some detail about FFB’s research projects, and explained how their organization funds and encourages gene therapy research being conducted by various biotech companies. Over the course of the last decade they’ve had great success in bringing to light important research being conducted at universities, and in convincing biotech and pharmaceutical companies (including global giants like Sanofi) that this research will bear fruit if private money is invested in it.
Ben Berman passed away in 1996, but his daughter Mindy Caplan, now 55, still works with the Foundation. Gordon Gund is a successful businessman despite the loss of his sight, and has ownership interest in several professional sports teams, including the NHL’s Cleveland Barons and the NBA’s Cleveland Cavaliers.
To support the Foundation Fighting Blindness, please visit their web site.
The Choroideremia Research Foundation
The genetic eye disease known as choroideremia (CHM) is rare, affecting fewer than one out of every 50,000 people, but it is believed to be the cause of 4 percent of all cases of blindness. Victims of this condition begin to experience night blindness in childhood, followed by the gradual loss of peripheral vision until they are completely blind.
For many years research into possible cures was hampered by the rarity of the condition, which made it difficult to secure funding for research, and by the animal testing problem: People who suffer from choroideremia lose their vision because they are unable to produce RAB Escort Protein-1 (also known as REP-1), but an animal model for testing was long unavailable because humans are the only animal that can survive without this protein—removing it from the genetic makeup of any other animal is fatal. Thanks to funding from the Choroideremia Research Foundation, however, this problem was solved in 2004 by Dr. Miguel Seabra, who was able to genetically engineer a mouse that could live without the REP-1 protein.
The Choroideremia Research Foundation was founded in 1999 by a computer student named Jason McKinney who was losing his vision to choroideremia and sought out others with his condition with whom he could correspond online. Fifteen years later, this organization is still working tirelessly to find a cure for choroideremia, operating largely out of the home of its Operations Manager, Cory MacDonald (himself a choroideremia sufferer), who generously took the time to give us the following e-mail interview:
EHW: I note with some interest that your web site’s account of CRF’s early days discusses other directions you might have taken, such as lobbying Congress for research funding or affiliating with the Foundation Fighting Blindness. I’m curious to know whether either of those actions has ever been considered since then — particularly Congressional lobbying. Has there ever been any government funding for CHM research?
On an organizational scale, no. We have had several individual members contact their local representatives and they all received the same answer: that Congress designates bloc grants to the NIH [the National Institutes of Health] and it is the NIH which makes the decisions on what research to fund. As for the FFB, although we are not officially affiliated with them, we do have quite a bit of contact with them and work together on funding research projects for Choroideremia. For example, we both provided non-overlapping funding towards Dr. Miguel Seabra’s development of the CHM mouse model.
EHW: I was fascinated to learn from your site that the animal testing problem was solved in 2004 with Dr. Seabra’s genetically modified mouse. It would be interesting to learn what fruit this development has borne since Doctors Seabra and Bennett began working on it (if it can be put into layman’s terms).
MacDonald: Let me note before I answer this question how tricky it was to engineer that mouse. You see, due to our genetic defect, we do not produce a certain type of protein called RAB Escort Protein-1, or REP-1. This protein is absolutely necessary for the day-to-day operations of every cell in our bodies. Without it, cells cannot take in nutrients, process them, or excrete waste products. Luckily, we also produce a protein called REP-2, which takes over the job of REP-1 when it’s not there. For some unknown reason, REP-2 is not expressed in the three layers that make up the back of our eyes, which is why our cells deteriorate over time, die off, and we lose our sight.
Now here’s where it gets REALLY interesting … Soon after mapping the CHM gene in the late 80s, Dr. Franz Cremers tried to create a CHM mouse model … [but t]he developing mice died in vitro. Come to find out, we are the ONLY animal in the world that produces REP-2, so if you remove the gene that produces REP-1, nothing works. In computer terms, it would cause a complete unrecoverable system crash.
Dr. Seabra and his team were able to get around this sticky situation by [figuring] out a time during the development of the mouse fetus where they could knock the gene out and the mouse would survive. Obviously, it’s a lot more complicated than that, but I’m sure you get the idea. It took several years for them to do this.
What was the significance of this step? Before 2004, researchers had nothing to work with on CHM, other than just running tests on us “CHMers” and watching how things developed. Therapies or cures for CHM were not discussed because they required some model other than a human to test on first. When Dr. Seabra and his team developed the mouse, it opened up lots of doors for research.
Now to finally answer your question about the fruits of Dr. Seabra’s mouse model. As I type this, Dr. Robert McLaren is over 2 ½ years into human genetic therapy trials for CHM over in the UK. Similar trials are expected to start here in the USA this year with Dr. Bennett and in Canada with Dr. Ian MacDonald [Editor’s note: no relation]. Dr. Seabra is working with the mouse in an attempt to develop a replacement therapy as well—and given the success (so far) with the UK trials, I’m extremely confident this will happen.
EHW: Let’s talk about Team CHM, the athletes working to raise money and awareness: is your organization directly involved with organizing this, or are they an independent group that has chosen you as the recipient of the funds they raise?
MacDonald: Team CHM is the brainchild of Danny Boren, CHMer and CRF Board member. So yes, this is a homegrown thing. We are recruiting CHMers, their friends, family members, and anyone else who wants to help us win the race against blindness.
EHW: You said your own struggle with CHM goes back to 1968; was any worthwhile research being done at that time, or in the 30 years between then and the formation of CRF?
MacDonald: Research? It depends on your definition. My test results, which established the baseline for progression rates among young CHMers, could be termed research I guess. Personally, considering the fact these tests were not performed with an eye towards a treatment or cure, I would term them more of a “learning experience” for the doctors who were interested in CHM.
When I was diagnosed at the age of 4, I was the youngest person ever found with CHM at that time. Bear in mind this was 1968, long before there was a blood test to diagnose it. The only reason it was found in me was that I had a cousin (Bobby, mentioned above) who was 24 years older than I. He was diagnosed first. They didn’t know a lot about CHM back then, but they DID know it was X-[chromosome] linked, so everyone in my family was called in for testing. Although I wasn’t showing symptoms at 4, the doctor was able to see the beginnings of the deterioration when he looked in the back of my eye. His diagnosis was confirmed in 2007 with genetic testing.
So, because I was so young, I made for a good study patient … my test results throughout my childhood and adolescence have been published everywhere over the years. Outside of that, in the late ‘90’s, Dr. MacDonald developed the blood test to diagnose CHM. Again, depending on your definition of research, this was another step.
EHW: Thank you Mr. MacDonald. If you, the reader, would like to help The Choroideremia Research Foundation, you can donate by visiting http://choroideremia.org/get-involved/ .
The Cornea Research Foundation of America
Based in Indianapolis, the Cornea Research Foundation of America (CRFA) was founded in 1988 by Francis W. Price Jr., MD, who still practices in Indiana and remains aninternationally recognized ophthalmic surgeon to this day. CRFA’s mission is to support research and public education about corneal disease, corneal transplantation, and intraocular lens surgery.
In 1991 CRF assisted the US Food and Drug Administration with its studies of the excimer laser, which is now commonly used in LASIK eye surgery. More recently, in 2011, the Foundation announced a breakthrough expected to drive tissue rejection rates for corneal transplants down from 12 percent to 1 percent. This breakthrough came in the form of a surgical technique known as DMEK , in which, of the cornea’s three layers, only the damaged layer is replaced, rather than the entire cornea.
We recently interviewed CRF’s Director of Development, Jessica Dingledy, who was kind enough to answer a few questions via e-mail:
EHW: Thank you for taking the time to answer our questions, Jessica. We were interested to read on your site about your Foundation’s participation in various clinical studies, such as the FDA’s 1991 studies of the excimer laser. What was the nature of the Foundation’s participation? Was it funding-related, or was work done by scientists employed directly by the Foundation?
JD: Dr. Price was a principal investigator in the early laser refractive studies sponsored by VISX and Chiron to obtain FDA approval of these procedures in the USA. Through the Foundation, Dr. Price also has conducted several large physician-sponsored studies of laser refractive surgery.
EHW: Does the Cornea Research Foundation have its own research facilities, or does it work more by funding studies conducted by government agencies, universities, corporations, etc?
JD: The Foundation designs and conducts vision-related clinical research studies in partnership with Price Vision Group in Indianapolis. The Foundation maintains the largest cornea transplant database in America and has helped drive tremendous innovation in how corneal transplants are performed through detailed outcomes analysis. The Foundation disseminates its findings through presentations at eye meetings around the world [and in] over 200 leading peer-reviewed ophthalmic journals. Together with Price Vision Group, the Foundation participates in industry-sponsored studies of new drugs and devices to treat vision problems and collaborates with other leading medical institutions such as Case Western Reserve University, Indiana University School of Medicine, University of Illinois, Columbia University, etc. The Foundation also provides medical education courses for eye care physicians.
EHW: I was also fascinated to read about Dr. Price’s breakthrough in corneal transplant, replacing only the diseased layer of the cornea and thereby reducing rejection rates. Can you tell me what DMEK stands for? Are the untransplanted layers from donor corneas preserved for use in other procedures, or is that not possible?
JD: DMEK is the acronym for Descemet’s Membrane Endothelial Keratoplasty. Here is a link to a brochure that explains DMEK in more detail in comparison to a penetrating keratoplasty, which was the standard of care for most of the 20th century.
It is possible to use the residual corneal tissue for a different type of cornea transplant procedure and this is being done outside the USA, where the supply of donor tissue is limited. Thankfully, in the United States we have an efficient and well-developed eye banking system, which has done an excellent job of educating the public about the importance of tissue donation. For that reason we have a good donor tissue supply. On the other hand we have extensive regulatory requirements in the USA and these discourage the use of one donor tissue for two or more transplant recipients.
EHW: Your organization’s history and its mission are pretty well described on your web site, but is there anything else about the Cornea Research Foundation that our readers might find interesting, such as recent news, breakthroughs, or triumphs? Or sudden challenges you may be facing?
JD: To reduce the risk of transplant rejection, cornea recipients take daily steroid eye drops for prolonged periods of time to reduce the immune response to foreign tissue. With the advancement of surgical techniques like DMEK, not only are patients experiencing more rapid healing times and better visual recovery, they are also benefiting from less risk of rejecting the donor tissue because so little tissue is now being implanted. So we are evaluating whether we can safely reduce the use of steroid eye drops after DMEK. Over time, steroid drops can cause pressure problems, which can lead to glaucoma. In addition, they can be very expensive. These studies are ongoing and will change the landscape of post-operative care for cornea transplant recipients. We are only limited by our resources, and we are appreciative of all those who help make this research possible.