Dispatches from ARVO 2015 Day 4: To protect and preserve

May 11, 2015

by Jennifer Phillips, Ph.D.

Up to this point, the focus of the presentations I’ve attended here has been on interventions designed either to correct RP at the molecular or cellular level. The progress, while promising, is also slow and complex. We’re not there yet, and the question remains for people who have RP now, what can we do in the meantime?

A series of talks today presented data from studies asking that question, and more, directly, what specific and non-invasive ways are there to protect against retinal cell loss?

One talk presented new evidence on the importance of regulating DHA (Docosahexaenoic Acid) levels in photoreceptor cells to preserve eye health. DHA has been tested as a dietary supplement for eye health, and while the evidence for increased consumption isn’t splendid, consuming foods rich in DHA, like salmon, nuts, or kale, does no harm. That said, these new data take the focus off the available levels of DHA itself and shift it to the molecular modifications that are required for DHA to actually benefit visual function.

DHA consumed in foods or supplements is processed in the liver and delivered via bloodstream to places where it’s needed, most particularly the eyes and brain. Byproducts eventually make their way back to the liver for processing, and altogether this cycle can be considered the ‘long loop’ of DHA metabolism.

There is also a more local processing loop that occurs in the retina, where different forms of DHA are stored, released and recycled between photoreceptors and RPE cells. The activity of this ‘short loop’ is dictated by cellular responses to stress, as discussed in the Day 3 ARVO post about cell survival mechanisms.

Research from the Bazan lab showed that, when genes responsible for regulating DHA function in the retina are disabled, cells are less able to put DHA to use, and photoreceptor health suffers as a result. This was true even when DHA regulation at the systemic level (the ‘long loop’) was normal. Understanding more about how this regulation occurs at the local ‘short loop’ level will help reveal the specific molecular changes that occur in some forms of RP. It also underscores the value of a more comprehensive approach to treatment options that would involve not only making sure that the protective substance (DHA) is consumed at sufficient levels so that it can be delivered to the right cells via the ‘long loop’, but also the knowledge of how to regulate the ‘short loop’ in the photoreceptors and RPE for maximum protective benefit. Meanwhile, keep eating that kale!

The talk that followed the DHA information covered the protective benefits of exercise on visual function. Previous research by this same research group didn’t use a genetic model of retinal degeneration, but instead induced retinal degeneration in mice via light damage. Furthermore, they used mild shocks to compel the mice in the experimental group to exercise on a running wheel for a specified period of time. Reasoning that neither of these experimental conditions (light damage or shock-induced mandatory exercise) were particularly transferrable to humans, the follow up work made important changes to the experimental design, using a genetic model of RP and making exercise voluntary. For the experimental mice, they provided a running wheel in cages that the animals could use whenever they wanted. Control mice had a stationary wheel that they could jump onto, but not run on.

The results showed that, even though the RP mice in both experimental and control groups continued to experience retinal degeneration, the mice that exercised voluntarily had better visual acuity, more active photoreceptors, and better preservation of cone photoreceptors in particular compared to the control group. The researchers went a step further to figure out why this might be, and paid attention to a molecule that promotes growth of neurons in the brain and the retina, known as BDNF. The role of BDNF as a protective factor for retinal disease has been studied quite a bit, but the results of just adding more of this factor directly to the retina have not been spectacular in previous studies. However, natural levels of BDNF are known to rise after exercise.

The researchers in the RP mouse exercise study tested what would happen if they repeated the voluntary exercise experiment exactly, but blocked the activity of BDNF. The result was a loss of the improvements in visual function and cell preservation seen in the first experiment.

Are either of these mouse studies transferrable to human RP patients? We don’t have enough information to declare this definitively, but in simple cost-benefit analysis, a healthy diet and regular exercise are good ideas for many reasons. If preserving vision is yet another positive by-product of eating good whole foods and working up a sweat, so much the better. It’s certainly something to ponder if you’re looking for new motivation to get to the gym.

One more day of ARVO talks and posters awaits! It’s been a great meeting so far and I’ve enjoyed reporting the highlights to you.

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