Last week I visited my ophthalmologist and learned that my blindness is caused by a mutation to the CERKL (pronounced like circle) gene, which, it turns out, is oddly not specific to my damaged retinas. At Genecards.org I read, “CERKL (Ceramide Kinase Like) is a Protein Coding gene.” And on Wikipedia I learn that “ceramides are a family of waxy, lipid molecules,” and that kinase is an enzyme, but I’m still not sure what this all means. I’m the wrong kind of doctor!
About a year ago I had a first round of genetic testing that came back negative. They had looked for more common (though still rare) degenerative diseases of the retina like retinitis pigmentosa (RP) and Stargardt disease, and had shown that in the world of rare eye diseases, I have a doozey. Then a few months ago Dr. Tsang, my ophthalmologist at Columbia Medical Center, urged me to test again as great leaps had been made in the swiftness of identifying rare gene mutations. What might have taken two years to find in the last test, could now give results in a few months. That is exactly what happened. In a few months, I learned that my recessive mutation takes place on the CERKL gene.
When I was a kid, I was diagnosed with retinitis pigmentosa (RP), though, through the years of degeneration, my symptoms hardly presented like a typical case. The symptoms of RP are generally a loss of night vision and far peripheral vision that gradually constricts through the decades, leaving the sufferer with tunnel vision that grows ever narrower. This means that people with RP can often read normal print long after they have need for a mobility aid, like a cane or dog.
Back when I was in my twenties and still living in San Francisco, I went to an RP support group and heard a man tell how he’d been waiting for the train in a downtown BART station reading a newspaper with his guide dog, when someone came up and told him, “You don’t look blind.” To appease the stranger, the storyteller put on his dark glasses. We in the group laughed very hard. (In such groups, a good amount of time is spent talking about how silly sighted people are.)
However, that man’s experience was not mine, and I felt a little envious. I wished I could still read normal print and run around with a cute guide dog. Instead, my weird version of retinal degeneration went in another direction. I lost some peripheral vision, and experienced night blindness–both of which signify damage to the rods, which make up the majority of our peripheral vision and sense light and movement. However, I also had a tiny chink removed from my macula–which is preserved until late stages in typical RP. Specifically my fovea, the central point of vision that consists of densely packed cones, which are the retinal cells that detect color and detail, blew out early on, making it impossible for me to read normal print. I could still make out large print for a long time if I placed it slightly off-center focus. Hence, I began to look askew at things in order to see them.
For me, it was only a few years between when I could not read the writing on the black board from the back of the class to when I could no longer read normal print. And yet, in many practical ways, I still looked and functioned perfectly normally. I could walk around without aid no problem, and that created a lot of confusion and shame.
As a person with a degenerative eye disease, I have experienced pretty much every notch on the sight blindness continuum, from normally sighted to nearly totally blind. In fact the vast majority of the world’s sight-impaired population is visually impaired, not totally blind. According to the World Health Organization ” 285 million people are estimated to be visually impaired worldwide: 39 million are blind and 246 have low vision.” However, these statistics tell us very little about what the individuals in either category see.
Doctors don’t tend to ask what I see anymore. An assistant may ask if I can see their hand waving in front of my face, but I have to tell them that I can still see the ceiling light if I place it in my periphery just so. In addition, they certainly never ask what has come to replace my lack of vision. Do they know that my visionscape presents a blast of fireworks–probably the explosive last gasps of the photoreceptors in my destroyed retinas–or the constant hallucinations curtesy Charles Bonnet Syndrome? Or that, when I’m tired I see less, or when drunk I see more, but when hungover less. When I am in familiar environments, my brain fills in information and I see more–just like the blind spot is filled in normal vision, so that, especially when I had more vision, I saw dramatically less when I was in unfamiliar places. For more on how the brain fills in vision, read Richard Gregory‘s classic Eye and Brain: The Psychology of Seeing.
Through my twenties and thirties my eye disease progressed in a haphazard way, but I still told people that I had RP, until recently, when I thought it seemed better, though more clunky, to describe my disease as a cone rod dystrophy, which explains the severity of the central vision loss at an early age.
It is a strange aspect of my slow march towards blindness that in the many years I spent as a visually impaired person, people often finished a conversation about my eye disease with the punctuation, “Is there a cure?” or “I’m sure they’ll find a cure.” Now that I’m basically a blind person, no one says anything about curing me. Of course, this could also be because I’m older. In any case, the irony is that now that I am older and blinder, there actually are glimmers of cures on the horizon.
From gene therapy to nanotechnology the possibilities of cure or cyborg-like augmentation are numerous and the darlings of the media. If you don’t believe me, check out the September 2016 National Geographic’s cover story “The End of Blindness.”
For about ten years, I did not have anything to do with eye doctors. It seemed to me useless. They simply confirmed the problem, but could offer no solutions. Then I started to get the feeling that things might be changing. Stem cell approaches were beginning to be a reality, even in the US, where stem cell research had been squelched by Bush and will likely be squelched by this Hydra in the White House, if the prolife heads prevail.
But now, with my CERKL gene identified as the culprit, I learn that curing my eye disease may have greater possibilities than stem cell therapy. In a CUMC blog post about his research Dr. Tsang is quoted as saying,
“Although gene therapy has shown promise in RP, it is complicated by the fact that defects in 67 genes have been linked to the disorder, and each genetic defect would require a different therapy. … Our study shows that precision metabolic reprogramming can improve the survival and function of affected rods and cones in at least one type of RP. Since many, if not most, forms of the disorder have the same metabolic error; precision reprogramming could conceivably be applied to a wide range of RP patients.”
RP patients as well as those like me who have one of the 200 mutations associated with other retinal cell degeneration have reason to be optimistic in this approach, since the rarity of the underlying cause will be less of a factor. In terms of research funding and focus, this is very good news for people like me who have odd mutations.
Hence my eye disease is a symptom that may be treated with drug therapy that may relate to many other kinds of problems. Dr. Tsang told me in the office that it may be treated with drugs someday, rather than surgery. In the article on CUMC’s blog he noted , “‘Further studies are needed to explore the exciting possibility that precision metabolic reprogramming may be used to treat other forms of RP and retinal degeneration.'”
The article mentions that some potentially therapeutic drugs may already exist to treat other conditions such as “enzyme blockers called thiomyristoyl peptides, a common plant pigment known as quercetin, and vitexin, a substance derived from the English Hawthorn tree.”
I personally really like the idea that hawthorn, a tree sacred to fairies, might someday provide me a cure!
For now, Dr. Tsang is recommending daily exercise, which has shown to be effective in slowing down the rate of degeneration in mice with RP. As one of Dr. Tsang’s assistants put it to me in an email:
“The article about SIRT6 found that, in mice with a similar retinal degeneration, better sugar metabolism (in the form of lactate) for the retina cells helped delay the degeneration. This is still in the animal/research phase of research so there is no specific recommendation we can provide based on this study right now. At this time we do not have a way to deliver lactate directly to the retina. However, daily exercise increases lactate transiently and was shown to be helpful for mice with a retinal degeneration. Since daily exercise is beneficial for many things anyways, we recommend it to our patients as perhaps it may also help their retinas too!”
Since exercise might have some impact on my eye disease, I thought I’d ask about diet, and Dr. Tsang recommended three servings of fish. I clarified, “A week right? Not a day?” He and his assistant laughed. “Then you smell like fish,” he said, which begs the question, would I be willing to smell like fish for a chance to see again?
The thought that all my terrible living has actually exacerbated my disease is unsettling. My whole life I’ve felt a victim of genetics, and now it turns out I may have accelerated my blindness by feeding the mutation with booze and youthful drug adventures, indifferent eating habits and not enough exercise. On the one hand it is good to know that I may be able to have an impact on how I see for the rest of my life and on the other, I am saddened at the thought that too much has been already lost, and that suddenly I find myself to be an author of that loss.
*This is Essay 10 of #52essays2017*