Restoration of useful vision: Dr. Edwin Stone's view

A few days back I had emailed Dr. Edwin Stone from the University of Iowa to congratulate him on the wonderful presentation he gave (see previous post). I wasn’t expecting any reply as I asked no question. Instead he wrote back, even thanking me for taking the time to let him know! A beautiful correspondence followed. He gave me permission to publish his email to me concerning the possibility of sight restoration to adults born with no vision, and on the usefulness of even very poor sight.

Here it is below. I’m sure it will be inspiring to many, not just because it’s so optimistic and positive, but above all for his sensitivity and kindness.

Fran
Dear Francesca,
Thanks for your most recent message.

Here is my short answer: I DO believe that some people who have been blind since birth will eventually be able to gain some useful vision from some type of surgical or medical intervention.

Why do I believe this?

1) Briard dogs with Leber's congenital amaurosis (LCA) who are old enough to be visually mature (that is, dogs whose cortical wiring is already complete) are able to regain very useful vision following injection of a viral vector with a functional RPE65 gene under the retina.

2) A 6 year old patient of mine with LCA who can see only hand motions at 1 foot is able to distinguish the border between her yard and her driveway when she is riding her bike. She can also distinguish the edges of doors and curbs bordering roads. She and her parents feel that all of these things help her to function in her daily activities -- that is, that her hand motions vision is "useful" to her.

3) Most patients with LCA have very healthy looking optic nerves even when their retinas look terrible. This suggests that if some new photoreceptive cells can be put into the retina (via some type of stem cell therapy) OR if the remaining ganglion cells can be stimulated (by some type of electrical retinal prosthesis) that the pathways from the eye to the brain are still healthy enough to carry useful information.

4) In 1996, we could identify the disease causing mutations in ZERO percent of patients with LCA. In 2005, we can identify disease causing mutations in over 50% of patients!

5) in 1984 (prior to the invention of the polymerase chain reaction) we could analyze a single gene for mutations in perhaps 5 to 10 people per year. Today, our laboratory can study a single disease causing region of a gene in 2500 people in a single day. This was made possible when a scientist named Kary Mullis figured out how a little microbe that lives in hot springs copies its DNA and then harnessed that microbe's DNA synthesizing machinery to do our bidding.

6) A tiny zebrafish egg with no visible structure to it can develop into an animal with a retina that is very similar in structure to a human retina in just 72 hours. All of the information needed to make a retina is in that little egg. I believe scientists will be able to learn some of the critical steps in this process and use that knowledge to convert stem cells into functional retinal cells for humans.

The points that I am trying to make are: vision doesn't have to be very good for it to be useful, restoration of vision in large visually mature animals who are "blind from birth" has already occurred, and the overall pace of research progress in the past 20 years is nothing short of breathtaking.

So why do some people say that people who are blind from birth will not be able to have their vision restored? Well, for one thing, all patients are different and a treatment that works for one person (or for a dog) may not work at all for another person. Thus, one cannot promise a given patient that they will recover some vision and they certainly cannot promise them that they will recover it by a certain date. (For example, in 1982, I spent 14 months analyzing 4000 base pairs of DNA from a single individual. I would not have been able to predict that the polymerase chain reaction was going to be developed just three years later and that that would allow us to analyze 4000 base pairs of DNA in 20 people in a single day).

I must say that I myself want to avoid suggesting that cures for retinal degenerative diseases are "just around the corner" because I honestly believe that there is still quite a bit of work to be done to develop useful treatments for most of these diseases. However, I also believe that these treatments will be developed and that in my professional lifetime some people who are born with a non-functioning retina will receive a treatment that will allow them to have ambulatory vision or better. To put it another way, I have hope that this will occur. My favorite definition of the word "hope" is "a desire accompanied by confident expectation". One needs hope in this business whether one is the doctor or the patient and I honestly think that we have lots of realistic basis these days for "confident expectation".

So, that was a long answer to a short but very good question. I appreciate your asking it.

Regards,

Ed