One Family’s Vision for Curing Blindness

Photos are courtesy of Dr. Elliott Sohn, University of Iowa Institute for Vision Research. The larger image is the fundus (i.e., the back of the eye). The insert is an OCT or optical coherence tomography retinal cross-section.

Buddy Lazier, 1996 Indianapolis 500 Champion, deserved a better day at the 100th running of the Indy 500, because he was driving in part to raise awareness for a great cause — curing blindness. Researchers at the University of Southern California Roski Eye Institute concluded recently that by 2050, 16.4 million Americans over age 40 will have vision impairments due to uncorrected refractive error compared to 8.2 million in 2015. More than 2 million over age 40 will be blind, and 6.95 million will have vision impairments. Professional sports offers a tremendous forum for raising awareness, and Buddy was kind enough to display the University of Iowa Institute for Vision Research logo on his racecar. The Institute is working with the Lazier family and my family for very personal reasons that I’m about to share with you. The Institute is on a much greater mission, using my words, to democratize treatment for the millions with inherited diseases of the eye.

“Buddy Lazier Sporting the University of Iowa Institute for Vision research Logo for the 100th Running of the Indianapolis 500” from the personal library of @InKenGray. All rights reserved (c) 2016 Gray Ventures, LLC.

The 100th running of the Indianapolis 500 was incredible, and not just because I got to cross the Indy 500 off of my bucket list. Members of the Institute Team who, in addition to using the event to raise awareness for their important work, met with us in Indianapolis just before the race to share some exciting developments about the inherited retinal disease that affects about half of the men in my mother’s family, including me. After years of work, they discovered the problematic sequence in our DNA that is the root cause of the problem. Before you can solve a problem, of course, you have to understand its cause.

Decades ago, I was a patient of the University of Iowa working to understand the pathophysiology of our family’s inherited retinal disease. In other words, we wanted to understand how and why our eyes function the way they do. Oversimplifying, I am a blue cone monochromat. My retina is dominated by one of the three types of color receptors, blue cones. A normal trichromatic person also has red and green cones. These “RGB’s” each sense a portion of the visible color spectrum and work together in people with normal vision. In my case, the RG’s are either absent or inactive. In addition to their color sensing duties, another role of RG’s is controlling rods, the retina’s low light receptors. Without RG’s, my rods are always on, always pulling in as much light as they can possibly get. All of this results in my vision being granular or pixilated — likely because the RG’s are not doing their jobs — and a color palette that is quite different from normal. I am also extremely light sensitive and react slowly to changes in lighting. This is an X-recessive trait meaning that the women in my family can pass it on to their male offspring. About half of us are affected. While I am one of the lucky mildly affected ones, the bad news is I am only correctable to about 20/150. The good news is the condition is stable and my night vision is excellent. Even better, the Institute Team just discovered the root cause!

Almost two years ago, my ophthalmologist, who did his residency at Iowa, suggested that I make a return visit for more tests. I resisted. The last experience was painful. I still have vivid memories of an electroretinogram (ERG) that measures the retina’s response to changes in light. A Clockwork Orange comes to mind. The good doctor explained that this trip would be different. We are focused today on the genetic root cause of your disease, he explained, not the mechanics. I still resisted.

Then we went on to hypothesize together what a return visit might mean.

  1. Since our disease affects a very small population, the problematic DNA sequence (the root cause) should be relatively easy to identify or at least be easier to find than diseases that affect a larger segment of the population.
  2. If we can identify the root cause, this may lead to a test that could determine whether or not a woman — thinking about my own daughter — can carry the disease to her male offspring.
  3. More importantly, a root cause can lead to a cure. While we had no expectations of solving this problem for the adults currently with this disease, finding the root cause is the first step toward a cure for the children in the family now, as well as the next generation.
  4. Perhaps even more importantly, given how rare this disease is, finding its root cause may lead to discovering the causes of and cures for other inherited retinal diseases.

How could I not be all in at this point? Off to Iowa we went!

As it turns out, the offending sequence of DNA very definitely was not easy to find. The research team quickly eliminated where the root cause “is not.” Then they focused their attention on where they thought the root cause had to be. After all, they had first eliminated the low hanging fruit. So now they focused their attention on the only other area of DNA heretofore known to contribute to inherited retinal diseases. Nothing. Nothing? Now they had to broaden their search. None of the known suspects were the root cause, so now the team had to essentially find a needle in a haystack. One of the researchers went on to say, “it was really more like finding a specific needle in a haystack sized pile of needles.” Ultimately, the team discovered that the root cause is a mutation in a sequence of DNA that requires relatively complex computational analytical ability to identify. That’s significant.

So where are we vs. our hypotheses?

  1. The first point in our hypothesis proved to be false. The root cause was very definitely not easy to find. This led researchers to discover a new place to search for the causes of other inherited diseases.
  2. We know these results will allow doctors to ensure women are well informed about the future of their male offspring. This is a manageable condition, more manageable if the family is prepared.
  3. We are closing in on a cure for the children in my family, and there is more and more unexpected discussion about significantly improving or partially repairing the vision of the currently affected adult population.
  4. Even more importantly, this is a significant discovery about the elements of our DNA that contribute to inherited retinal diseases. This will lead to more discoveries. More cures will follow.

How could I not be excited about this? So what’s next? Now that we understand the root cause, we plunge into finding the cure. I’m all in.

Dr. Elliott Sohn sat down with me the Saturday before the Indy 500 to announce that they have indeed isolated the problematic DNA sequence, the root cause of my disease. Everyone was pretty emotional, to say the least. The discovery could prove to be groundbreaking. The mutation causing the disease is in a location of the red-green cluster of DNA that is highly repetitive thus difficult to sequence without advanced genetic analysis. That fact alone has major implications for understanding other inherited retinal diseases.

My mother, asymptomatic brother, and I provided DNA samples to the Institute Team with the near term objective of finding a cure for the children in our extended family. The treatment, if administered early enough, can be used to prevent amblyopia — and the ‘lazy eye’ that can result in kids. In these children, the healthy eye is patched so that the brain develops information pathways and learns to use the weaker eye effectively. Once the weaker eye gains strength and the brain learns to process visual input from it, the patch is removed to restore binocular vision. In our case, the plan is to surgically introduce healthy retinal cells, grown from the child’s own DNA, directly into his retina. If done so at an early enough age — the University of Iowa Team believes nine years old or younger — the brain should develop the pathways necessary to manage the flood of data healthy retinal cells will provide.

The coming months and years will be devoted to validation with the extended members of my family who have the disease, refining the surgical procedure, completing FDA approval, and identifying candidates.

The unintended benefit of this research is researchers expect to restore some of the eyesight to those of us in this generation, perhaps to what we enjoyed as adolescents. While it’s unlikely we are young enough to develop the pathways needed for perfect vision, many of us may regain the best eyesight of our lives. In my case, for example, we are targeting an improvement from 20/150 to the 20/40 or 20/50 range. While that may prove to be unrealistic, it’s a great stretch goal. At the very least, we may be able to reduce my sensitivity to light, and that alone would be a huge win. I believe the first surgeries will focus on my generation to refine the process for the youngsters. We’ll see what happens next.

All rights reserved (c) 2016 Gray Ventures, LLC.

Dedicated to the memory of Ray Gullett.

Four days after the Indy 500, I had a terrific conversation with my late cousin Ray Gullett. Ray and I shared this disease and, equally importantly, a long-term vision for curing it for following generations. He was absolutely thrilled to hear about the Institute’s discovery. There are children in his family he suspected might be affected and said, “I’d give them both of my eyes to fix his.” As it turns out, Ray passed away just a few days later after succumbing to a long illness. He’s gone, but with the awareness that we know the root cause and we are on a path to the cure.

If you are compelled to help in their effort to cure blindness brought on by inherited diseases of the eye, please consider donating to the University of Iowa Institute for Vision Research. Please direct your support to:

ATTN: Katie Sturgell
University of Iowa Foundation
PO Box 4550
Iowa City, IA 52244–4550

You can focus your support on inherited retinal diseases by specifying fund number 305–19–000 for the Institute for Vision Research and Dr. Elliott Sohn’s team who recently discovered the cause of the inherited retinal disease that affected Ray and others in our family. You would do our family a tremendous honor if you specify that your gift be in memory of Ray Gullett.

To learn more about how your support will be used, please reach out to Katie Sturgell, Katie is a great person who can assist you within her role of Assistant Director of Development for the Institute for Vision Research.

I am passionate about serving on the Board of the Central Illinois Center for the Blind and Visually Impaired in its 61st year providing programs and services that meet the emotional, educational, and social needs of the blind and visually impaired community in Central Illinois.

It was my honor and privilege to serve as Caterpillar’s first Corporate Director of Innovation. There is absolutely no doubt the “Innovation Incubator” team we created will continue helping to reinvigorate the passion for innovation in this 90-year old iconic company.

You are welcome to follow me on LinkedIn or Twitter @inKenGray as the adventure continues.