PRA Research

How I Began My Research

Being a Libra, it's my fate to endlessly ponder the philosophical nuances of every situation.

If you're one of the rare people who finds out that your dog has prcd-PRA before he has any symptoms, you're in a very small club. In breeds where PRA is a known problem, breeding pairs are typically screened to prevent PRA puppies. Otherwise, you find out your dog has PRA when his vision problems are advanced enough to be detectable--either by a CERF exam, or through his own behavior. But dogs are experts at compensating for vision loss, so it's common for people to only realize that there's a problem after the dog has become completely blind.

In Trevor's case, the test for Goldens became available when he was a young dog. And thus I was handed a crystal ball that told me my dog was destined to go blind.

What this means in practical terms is that there is no body of information on how to deal with a young dog that has prcd-PRA. If you do an internet search for PRA, there is nothing to give you much hope. The disease is universally characterized as an inevitable process for which no treatment exists. The dog's photoreceptor cells are pre-programmed to die. The solution for PRA, according to every website, is to eliminate it through careful breeding. It all made sense, but what about Trevor?

I quickly realized that there was nothing in canine medical literature that could help me. But then I discovered a silver lining: PRA is genetically similar to a human disease called retinitis pigmentosa. Or as one study put it: "Identical mutation in a novel retinal gene causes progressive rod-cone degeneration (prcd) in dogs, and retinitis pigmentosa in man."

Because of this genetic connection, dogs are being used as proxies to study human retinal degeneration, and to test possible therapies. So that is the ultimate irony--whereas "no one cares about treating PRA" since the best way to eliminate it is through selective breeding, finding an effective treatment for retinitis pigmentosa is huge. And dogs are right in the middle of it.

As soon as I understood the connection, I knew that I should be searching on retinitis pigmentosa (RP). I described the beginning of this process in my blog post How I Spent New Years Eve.

My research about RP convinced me that even though PRA and RP are diseases of programmed cell death (also known as apoptosis), there were ways to delay the onset (update 8-19-09: see the conclusion in this article for a discussion of how photoreceptor cell death is different from classic apoptosis). But as always, the devil is in the details. Vitamin A palmitate has been shown to delay RP progression in some percentage of human patients. But this is where it gets tricky, because you can't generalize across species. This especially seems to be true when you're talking about Vitamin A, Vitamin E, and DHA (fish oil), which are powerful agents that often seem to confound researchers by not having the expected results in trials.

Should dog owners mimic what human RP patients do to delay onset? The answer turns out to be no, not necessarily. Contact me personally if you want more background on this.

A Tip on Gathering Medical Information

I joined the retinitis pigmentosa Yahoo! group as a way of learning more about RP. One of the members shared a great technique for following the latest research: set up a Google Alert to send you regular email on news stories containing your keywords.To set up a Google Alert:

    1. Go to http://www.google.com/alerts.
    2. Enter the search terms for which you want to receive alerts. I created separate alerts for "progressive retinal atrophy" and "retinitis pigmentosa".
    3. Specify the type (news, blog, etc.) and frequency of the alert. By default, the settings are comprehensive (i.e., send me results from all available sources) and daily.
    4. Enter the email address you want the alerts sent to.
    5. Click Create Alert.

This was an interesting exercise for me to go through, because I immediately realized the following:

    • There is a tremendous amount of research going on for RP--everything from diet/supplements to implants to stem cell therapy. Not a week goes by without at least a few exciting new developments.
    • The story never changes on the PRA side. All you get is the echo chamber of the internet, repeating the same warmed over cliches on thousands of websites.

Moral of the story: if you think outside the box even a little, there's a whole other reality out there.

RP Treatment: General Topics

2010

2008

This is a good synopsis of treatments for retinal degeneration. It's a presentation that was given by Dr. Gerald J. Chader at the 2008 VisionQuest conference:

Present and Future Treatments for Retinal Degenerative Diseases

This is where I learned about RetinaComplex, which is currently being tested in an RP clinical trial. I've started giving this to Trevor. According to this VisionQuest synopsis from October 2008, "Results from this trial are not yet available but after one year of progress, the unofficial reports are favorable." (page 8)

Here is the original rodent study that led to the human trial.

PRA and RP Research Links

Here are some links for more information:

Researchers

Research Based on Diet/Supplements

Those given lutein had a slower loss of vision in the mid-peripheral visual field. Peripheral vision is the area of sight that occurs outside of the very center of vision. In RP, sight is generally lost in this region first as symptoms progress. The researchers estimated that visual sensitivity could be preserved for an additional three to ten years with lutein supplementation.

Purpose:

In a previous controlled clinical trial,1 it was shown that short-term saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration (AMD). The aim of this longitudinal, open-label study was to evaluate whether the observed functional benefits from saffron supplementation may extend over a follow-up of one year.

Methods:

Twenty-nine early AMD patients (age range: 55-85 years) with a baseline visual acuity > 0.5 participated in the study. They underwent clinical examination and a Focal ERG (F-ERG)-derived macular (18°) flicker sensitivity estimate1 every three months over a 12 month period of treatment (saffron 20 mg/day) and follow-up. Visual acuity and F-ERG sensitivity, derived from the estimated response amplitude thresholds, were the main outcome measures.

Results:

After three months of supplementation, mean visual acuity improved by two Snellen lines compared to baseline values (0.75 to 0.9, p < 0.01). Mean FERG sensitivity improved by 0.3 log units compared to baseline values ( p < 0.01). These changes remained stable over the follow-up period.

Conclusions:

These results indicate that in early AMD saffron supplementation induces macular function improvements that remain stable at least for one year after starting the treatment.

In the placebo group the Multi focal ERG readings taken at the beginning of the study showed a statistically significant difference to those taken at the end of the 12 month period. Patients receiving Retina Complex showed no statistically significant difference between the two sets of data. This confirms that there is a SLOWER progression of disease in the treated subjects compared with those getting only placebo.

The effects of green tea catechins in reducing harmful oxidative stress in the eye lasted for up to 20 hours, the study says.

Research NOT Based on Diet/Supplements

Cell death in inherited retinal photoreceptor degeneration has

often been understood as apoptosis. However,

there are considerable differences between classical apoptosis

and photoreceptor cell death, suggesting the action of

non-apoptotic cell death mechanisms. Based on evidence

collected in recent years, we propose an alternative

molecular pathway as a cause of photoreceptor cell death.

Importantly, this pathway shares none of the major

characteristics of classical apoptosis... This

may have far-reaching implications for the design of

therapies for diseases that, like RP, affect photoreceptors.

While therapeutic approaches aimed at classical apoptosis

have so far been only moderately successful at best, the

recognition that non-apoptotic processes are involved may

open up new avenues and provide a number of new

therapeutic targets.

New! Here is another link that talks about how cell death in RP is not classical apoptosis: Retinitis pigmentosa: a new form of cell death (June 14, 2011).