We Orioles fans appreciate that Adam isn’t marveling at how well his eyes are tracking the ball during its quick, 300-foot journey. That, of course, might distract him from catching it.

But for many researchers fighting blindness, understanding the complex process of vision, and how the retina makes it possible, is their game.

Take, for example, Erika Ellis, a medical student at the University of California, San Diego, and Howard Hughes Medical Institute research fellow, who is receiving a one-year career development award from FFB to study retinal ganglion cells. Erika will be researching how these cells refine and package visual information and send it through the optic nerve to the brain, where the final images are created and interpreted.

While the process of seeing begins when photoreceptors convert light into electrical signals, it’s up to many other types of downstream retinal cells — including ganglion, amacrine and bipolar cells — to contextualize and enhance the signals so we can perceive motion, contrast, edges and boundaries and other visual details.

Researchers like Erika are particularly interested in how ganglion cells map to different regions of the brain. There are approximately one million axons — fibers in the optic nerve — connecting the retina’s ganglion cells to the brain, so the task is daunting. But documenting the brain-retina relationship will enable experts to better understand how they work together and how well emerging retinal treatments are restoring vision.

Ganglion cells are also an attractive target for vision-restoring treatments, because they survive long after photoreceptors degenerate from diseases like retinitis pigmentosa and macular degeneration. Emerging optogenetic therapies are designed to empower ganglion cells to respond to light, so they can function somewhat like photoreceptors and restore vision. While their research is at an early stage, it holds promise for people who have lost their photoreceptors to the most advanced retinal conditions.

If you are interested in learning more about ganglion cells, optogenetics and the Foundation’s diverse research portfolio, there’s still time to register for our VISIONS 2013 conference, taking place in Baltimore June 27-30. You’ll also get the opportunity to meet nearly 50  of the Foundation’s research all–stars.

And if you happen to be a baseball fan, the Yankees are also in town that weekend, playing at Camden Yards, right down the road from the conference hotel. Come root for Oriole standouts like Adam, Chris Davis, Manny Machado, Matt Wieters and Nick Markakis. The Yankees have some players as well, but I can’t recall who they are.

Pictured, top, Baltimore Orioles centerfielder, and Golden Glove recipient, Adam Jones; and, above, HHMI-FFB Medical Fellow Erika Ellis.

Want to know about gene therapy? Our playlist features four videos, one each from four renowned researchers, including Dr. Eric Pierce, chairman of FFB’s Scientific Advisory Board, who does a great job summing up the vital role research plays in finding treatments and cures:

We also offer playlists covering stem cell therapy and gene discovery. And you won’t want to miss the video on why making donations to FFB’s research is so important at this crucial time:

To view all of the Foundation’s playlists, click here.

The findings reported in a recent research paper from the University of Utah on autosomal dominant Stargardt disease are a great case in point. But before I discuss the new research, which was funded by the Foundation Fighting Blindness, let me give you a little background on this story. One word of warning – as my professional vernacular is loaded with acronyms, I’ll be serving alphabet soup with this post.

Stargardt disease affects approximately 30,000 people in the United States and 40,000 in Europe. A vast majority of the cases, about 95 percent, are autosomal recessive and mainly caused by mutations in the ABCA4 gene.

The other five percent are autosomal dominant, most of which are caused by defects in the gene ELOVL4. This form of disease is often referred to as STGD3. The University of Utah paper is specifically about new findings for ELOVL4 mutations.

In 2001, Foundation-funded researchers found that ELOVL4 was linked to STGD3. They also knew that ELOVL4 was involved in the production of very long chain polyunsaturated fatty acids (VLC-PUFAs), and suspected that a lack of those fatty acids was detrimental to retinal health. Humans get VLC-PUFAs by consuming their precursors, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are abundant in coldwater fish, as well as fish-oil and algal supplements.

In 2007, the University of Utah’s Dr. Paul Bernstein began a clinical trial of DHA and EPA supplementation for people with STGD3 to see if it would slow their vision loss. His observations of a Utah family with ELOVL4 mutations suggest that DHA and EPA supplementation might do so. In 2006, his group published a retrospective analysis, which found that the family members who had most EPA and DHA in their diets had the mildest retinal changes.

But alas, as we seem to be on a logical path forward for treating STGD3, a team of scientists from the University of Utah — which included Drs. David Krizaj, Peter Barabas and Bernstein — found that mice lacking VLC-PUFAs in their photoreceptors did not have retinal degeneration or associated vision loss. It appears to be a classic “one-step back” moment.

Now, these findings come with a major caveat (not to be confused with caviar, which, interestingly, is high in DHA and EPA). This new research is based on mouse models, which are by no means perfect replications of human STGD3.

However, the new study also suggests that ELOVL4 may be involved in something more than the production of VLC-PUFAs, and that “something” may also be linked to STGD3. More Foundation-funded research is underway to get a better picture of what causes STGD3.

Ultimately, Dr. Bernstein’s prospective clinical trial, which will conclude later in 2013, will tell us more about the role of DHA and EPA in STGD3.

In the meantime, comrades, I encourage you to check out my previous blog post on DHA and EPA, which discusses how these healthy fats have exciting potential for treating a wide range of retinal degenerations and other health conditions.

Pictured, above: Dr. David Krizaj (Photo courtesy of Dr. Bryan Jones, retinal neuroscientist at the University of Utah.)

Ultimately, it is as important to design a good clinical trial as it is to develop a good treatment. We could have the best treatment ever devised, but without a good human study to demonstrate its safety and efficacy, we’ll never obtain U.S. Food and Drug Administration approval, to get it to the people who need it.

Designing a clinical trial for retinal disease therapies is challenging for many reasons. First, retinal diseases often progress slowly and affect vision in ways that are not easy to measure. Often, evaluating visual acuity by having someone read an eye chart doesn’t tell us if a treatment is actually saving vision. We may need to look at the person’s peripheral vision or ability to adapt to dark settings.

Observing structural changes in the retina itself may enable us to more quickly determine if a therapy is benefiting vision. Figuring out the best “outcome measures,” as we call them, for use in a clinical trial is one of the most important goals of ProgSTAR.

ProgSTAR will also help identify the best potential participants for a clinical trial of a Stargardt disease therapy. Will people with early-stage or late-stage disease be more likely to respond to a therapy?  How long will we need to monitor them to observe a response? We need answers to these questions to implement treatment studies that are cost-effective and expedient.

Not only do we need the right patients for a clinical trial; we need good clinical researchers. The Foundation has assembled the world’s best Stargardt disease experts for ProgSTAR. Led by Dr. Hendrik Scholl, of the Wilmer Eye Institute at Johns Hopkins, these investigators are unmatched in their understanding of Stargardt disease, and participation in the study will advance their knowledge even further. Dr. Patricia Zilliox, the Foundation’s chief drug development officer, serves as project director. She is well-qualified, with more than 30 years of industry experience.

ProgSTAR is monitoring approximately 200 people enrolled at nine clinical centers. They will be monitored for two years, but researchers are also looking at retrospective data on patients to get a better picture of how the disease and vision loss progress. ProgSTAR is a “by invitation-only” party; investigators are recruiting only their existing patients to participate.

It is rare for a non-profit foundation to fund a natural history study, because they are expensive — ProgSTAR will cost at least $3 million — and they don’t provide an immediate return of a new therapy. But, as I’ve just explained, these studies are invaluable for moving treatments forward for inherited retinal diseases; they bring us a big step closer to a cure.

Pictured, above: Dr. Hendrik Scholl conducts an electroretinogram, or ERG, with a patient at the Wilmer Eye Institute.

What’s signficant about many emerging neuroprotective therapies for the retina is that they have the potential to treat a wide range of diseases, regardless of the genetic mutation causing vision loss. With about 200 genes linked to retinal diseases, this is a huge plus. They might also be used in conjunction with a genetic therapy to enhance its vision-saving effects.

Though neuroprotection usually isn’t addressing the root cause of the disease, it may be nearly as beneficial as a permanent fix, if useful vision can be saved for a person’s lifetime.

Neuroprotective treatments are being developed in many forms — proteins, drugs (small molecules) and nutrients. And there are several ways to get a neuroprotective therapy to the retina, including eye drops and oral medications.

Imagine having a therapy factory in the retina — in the forms of transplanted cells or genes — that provides continual release of neuroprotective proteins. Well, researchers are working on those, too.

Here are three examples of emerging neuroprotective therapies for the retina:

Protecting Mitochondria — MitoChem Therapeutics, a Foundation-funded  start-up company, has identified two compounds, which show potential for saving vision for people affected by several retinal diseases, including retinitis pigmentosa (RP), cone-rod dystrophy, Bardet-Biedl syndrome, Usher syndrome, Stargardt disease and age-related macular degeneration (AMD).

The compounds work by protecting mitochondria, the power supplies for all cells in the body, including those in the retina. Investigators have refined the compounds to the point where they save virtually all of the photoreceptors in a mouse model of retinal degeneration. They’ve also demonstrated that eye drops can effectively deliver large amounts of one compound to retinas in eyes comparable in size to those in humans. Eye drops are beneficial, because they minimize potential systemic side effects.

Docosahexaenoic Acid (DHA) — DHA is an important structural component of cells in the brain and the retina. It appears to have many neuroprotective properties and is prescribed for a variety of conditions, including heart disease. Perhaps most relevant to retinal degenerative diseases, DHA can reduce the destructive effects of inflammation and oxidative stress. It also helps maintain the structure and metabolism of photoreceptors.

The Retina Foundation of the Southwest is completing a Foundation-funded clinical study of DHA for males with X-linked RP. Previous clinical studies conducted by Dr. Eliot Berson show that vitamin A combined with DHA can slow vision loss in people with RP. In 2014, the National Eye Institute will complete a clinical study of DHA and other nutrients for people at risk of advanced AMD. DHA can be obtained by eating salmon, tuna and other coldwater fish, or by taking fish-oil or algae supplements.

Rod-Derived Cone Viability Factor (RdCVF) — Drs. José Sahel and Thierry Léveillard, of the Institut de la Vision in Paris, received the Foundation’s Trustee Award for their discovery of Rod-derived Cone Viability Factor (RdCVF), a protein that preserves and rescues cones, the cells in the retina that provide central and color vision. They are now developing a gene therapy that provides sustained delivery of RdCVF after a single treatment. The protein could be beneficial to people affected by a broad range of retinal diseases, including several forms of retinitis pigmentosa. With Foundation funding, the researchers are working to move their RdCVF gene therapy into a clinical trial.

There are several other emerging neuroprotective therapies in the Foundation’s research portfolio. Stay tuned to Eye on the Cure and the Foundation’s website for updates on these emerging cross-cutting treatments.

Pictured, above: Some neuroprotective therapies may be delivered by eye drops. (Photo courtesy of the National Eye Institute.)