CERKL Gene: My Newly Identified Eye Disease Is Not an Eye Disease, Essay 10 of #52essays2017

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. Read my previous essay “Laurel Wreaths: A Brief Hydrosol Encounter” here*

Share Button

In the Beginning Were the Eye Doctors, essay 1 of #52essays2017

Before the base closed to make way for the National Park, Lucasfilm, and the Thoreau Center, my mother and I drove regularly through the Presidio to buy cheap groceries at the commissary or to the Letterman Army Medical Center for visits to the pediatricians and then many eye doctors. My dad was in the military, and as a dependent, I received benefits that extended beyond my parents’ divorce.

Letterman Army Medical Center photographed from above with the Golden Gate Bridge in the background. (Wikipedia)

I loved the drive that took us through the Arguello Gate, punching our car into an enchanted forest of Monterey pine, Monterey cypress, and the Tasmanian bluegum, a eucalyptus all the way from Australia. I did not know their names then, or that these seemingly primordial trees had been planted but a hundred years earlier. Inspired by the success of Golden Gate Park and Planted by the U.S. Army, these trees were meant to beautify the windswept brush lands that were an eyesore to the San Francisco Bay newcomers. It was no accident that the sudden woodlands reminded me of the enchanted New England greenery I looked longingly at in my mother’s pictorial atlas of America. The easterners who came to take over the Presidio after the Mexicans did not appreciate the sandy bluffs blowing into their windows or the scrubby barrenness sweeping down to the bay. So they made that landscape familiar by planting thousands of trees. And in those trees they nestled their Georgian Revival buildings for my mother to point to, with all the authority of having, for a few years, been the wife of an officer, “That’s the house of a general.” Or “those are bachelor quarters,” and I was duly impressed. One of those exotic brick buildings is now a boutique inn for tourists looking to enjoy amenities and hiking trails.

but this was the early ’80’s, at least ten years before the base was decommissioned, and long before I had need to know that the landscape was man-made. To my keen young eyes, it looked ancient, as if it were what San Francisco looked like under or behind all the people and buildings–prehistoric, darkly enchanting and full of dappled light. I could not know it was all fakery beyond those gates, all artifice and make believe.

 

In fourth grade, I suddenly couldn’t see the writing on the blackboard from the back of the class. I told my mother and she made an appointment at the optometrist. I was excited. Getting glasses seemed to me to be very grown up. We drove to one of the bungalows that lay in covered strips with wooden steps leading up to planked covered walkways, almost like an Old West town. The building was dark and creaky. I sat in the big chair and looked through the tiny eyeholes in the cartoonishly huge lens machine. I could not read the small print on the chart. Still, no matter how many times the lenses shifted and the doctor asked, “tell me if this one is better,” (click) “or this?” (click) “this one, or this one,” the line did not reveal itself to me. I was a child who wanted to please, so I tried very hard to see a difference. “Maybe, a little better.” I’d say, but there seemed to be no difference in any of the shifting lenses–no better anyway, only worse. Many of the lenses made my vision blurry. I did not know how to explain then that my vision had not been blurry before. I have never lived in a blurry world. My eye problems have nothing to do with focus. It was always a question of a lack of information, of a pixilated visionscape, of television fuzz, but I hadn’t the words then, or even much of all that was to come.

The optometrist prescribed some glasses, though he sheepishly explained that he could not get my vision down to 20/20. They did nothing to help me see the writing on the blackboard.

We went to another optometrist and then maybe an ophthalmologist. Again, there was the same clicking of lenses with its odd attendant sensations of shifting air currents so close to the eyeball, with no luck. “Maybe a little better.” Or “worse,” was all there was for me to say. After a long time, the eye doctor called my mother in and told us that he could not correct my vision.

Perhaps it was that doctor, or perhaps the next, possibly to allay my mother’s fears or perhaps to mitigate his own impotence, said, “Her eyes are growing too fast for her body.” Or maybe he said that my body was growing too fast for my eyes. That satisfied us for a little while.

Finally, we were referred from the bungalows to the main hospital–the building that has since been demolished to make room for the Letterman Digital Arts Center–to see the head of ophthalmology. This was when my mother began to worry that something queer and a little scary might be going on. Though My vision loss was not very impressive, maybe 20/40 in the worst eye, the head of ophthalmology could not offer a solution either. He sent me out of the room to talk to my mother, to berate her for bringing me to him.

In response to my mother’s worried summery–eye doctors offering wacky opinions and no answers–this brilliant man spoke lamely and with spite, “Maybe she can’t see because you’ve been taking her to so many eye doctors.”

This summit of ludicrous subterfuge, this apotheosis of smug defiance in the face of ignorance has oft been repeated by my mother and myself (who was loitering just outside the door, listening) as the climax in our sad little detective story: What was killing my sight?

My mother, never good at checking her emotions, allowed her voice to rise with tears and said, “then why can’t she read the writing on the blackboard?” She would not accept another answerless dismissal. To his credit, he did not dig in, but relented, perhaps embarrassed deeply, though on the surface the coolness remained. He called me back into the room and took another look into my eyes, with his headlamp and magnifying monocle, and saw…something. I can only imagine that it was a blip on the landscape of my retinas, a suggestion of that dystrophy that would grow into eventual blindness, or it may be that he saw nothing, but suspected something, something remembered from medical school or read about in an ophthalmology journal. Perhaps it was a eureka moment that sparked the intelligence of this head of ophthalmology–an intelligence that had been momentarily dimmed by ignorance. Maybe it was then that he remembered a degenerative eye disease called retinitis pigmentosa (RP), or maybe it was later, but, in any case, the diagnosis would be forthcoming, and one which I would use for decades.

As it turned out, my eye disease did not present like RP–I lost my central vision first whereas most people with retinitis pigmentosa lose peripheral vision first, so that as it progresses, they experience an ever more restricted tunnel vision. My disease progressed from the center outward, albeit jaggedly, leaving pockets of living cells.

Thirty some odd years later, I’ve learn that my cone-rod dystrophy is caused by a gene mutation that remains unidentified. In a world of rare eye diseases, I have a really rare one. As I write, my blood is going its second round of genetic testing, and it may be that I have a mutation all my own.

Back then, a diagnosis of retinitis pigmentosa was at least a name, a thing I could tell people, and it was rare enough and unique. I was strangely proud, so that when at the end of that first year, I was sent across the road to the Letterman Army Institute of Research (LAIR) for observation and experiment, I was excited. For three days they ran me through a battery of tests–from organizing little disks of gradient colors to a primitive electroretinography (ERG), putting me into a dark room to measure the electronic firings of the photoreceptor cells in my retina. The ERG is standard procedure at retinal specialists now, but they were just figuring it out back then.

In my most recent visit to the ophthalmologist, after dilation and numbing drops a technician laid thin wires along each of my bottom eyelids and taped the ends to my cheeks and forehead to keep them in place. The thin wires were then connected to thicker ones that in turn made their way into a computer. But that first ERG, a lab rat was I, laying in the dark for many hours with my eyelids held open by grotesque contact lenses from which the wires sprung. That had been perhaps the scariest, but also the most important test I underwent at LAIR, one that likely contributed to the current state of the art technology that even suggests the possibility of a near-future cure.

I subsequently did a presentation on the experience. By that time, I’d moved from fourth grade to fifth grade, and in my private girl school, that meant a change in uniform, from green plaid bib dresses to sailor-style middies and pleated navy skirts.

My presentation on retinitis pigmentosa and my battery of testing at LAIR, with its photographs and little moments of humor, like when I described looking into a contraption to click a button when I saw (and did not see) a tiny red light move into and out of my visual field, as resembling nothing so much as staring for hours into an illuminated toilet bowl, got a laugh from my classmates. I also got some pointed questions from my teacher. Perhaps she, along with my other teachers, was concerned, but they did not let on. It was a small school and I was a scholarship child in a sea of very rich girls, so there was perhaps a lot of feeling sorry for me going on. Or perhaps not. Maybe it is just my grown up self who feels sorry for that little girl who tried so hard to make light of something scary and totally out of her control. Out of even the control of her mother and teacher’s and eye doctors too.

Image of Godin's retina in 1983

The progress of my eye disease has been the degeneration of my sight–progress and degeneration have thus been strangely confused in my mind since I was a kid. And today, it is not clear to me whether this long eye progression of sight to blindness, the slowest of calamities, akin to aging in its relentless and somewhat boring degeneration, has diminished or enhanced my life experiences. But human existence being what it is–complicated and fleeting–I imagine the answer must be both.

 

*This is the first of #52essays2017 written with all four senses and remembered sight. Read more about the project and the woman behind it HERE*

Share Button