Team finds a new structure in dogs' eye linked to blinding retinal diseases

March 6, 2014

In humans, a tiny area in the center of the retina called the fovea is critically important to viewing fine details. Densely packed with cone photoreceptor cells, it is used while reading, driving and gazing at objects of interest. Some animals have a similar feature in their eyes, but researchers believed that among mammals the fovea was unique to primates—until now.

University of Pennsylvania vision scientists report that dogs, too, have an area of their retina that strongly resembles the human fovea. What's more, this retinal region is susceptible to genetic blinding diseases in dogs just as it is in humans.

"It's incredible that in 2014 we can still make an anatomical discovery in a species that we've been looking at for the past 20,000 years and that, in addition, this has high clinical relevance to humans," said William Beltran, an assistant professor of ophthalmology in Penn's School of Veterinary Medicine and co-lead author of the study with Artur Cideciyan, research professor of ophthalmology in Penn's Perelman School of Medicine.

"It is absolutely exhilarating to be able to investigate this very specialized and important part of canine central vision that has such unexpectedly strong resemblance to our own retina," Cideciyan added.

Additional coauthors included Penn Vet's Karina E. Guziewicz, Simone Iwabe, Erin M. Scott, Svetlana V. Savina, Gordon Ruthel and senior author Gustavo D. Aguirre; Perelman's Malgorzata Swider, Lingli Zhang, Richard Zorger, Alexander Sumaroka and Samuel G. Jacobson; and the Penn School of Dental Medicine's Frank Stefano.

The paper was published in the journal PLOS ONE.

The word "fovea" comes from the Latin meaning "pit," owing to the fact that in humans and many other primates, the inner layers of the retina are thin in this area, while the outer layers are packed with cone photoreceptor cells. It is believed that this inner layer thinning allows the foveal cone cells privileged access to light.

It is known that dogs have what is called an area centralis, a region around the center of the retina with a relative increase in cone photoreceptor cell density. But dogs lack the pit formation that humans have, and, before this study, it was believed that the increase in cone photoreceptor cell density didn't come close to matching what is seen in primates. Prior to this study, the highest reported density in dogs was 29,000 cones per square millimeter compared to more than 100,000 cones per square millimeter seen in the human and macaque foveas.

It turns out that previous studies in dogs had missed a miniscule region of increased cell density. In this study, while examining the retina of a dog with a mutation that causes a disease akin to a form of X-linked retinal degeneration in humans, the Penn researchers noticed a thinning of the retinal layer that contains photoreceptor cells.

Zeroing in on this region, they examined retinas of normal dogs using advanced imaging techniques, including confocal scanning laser ophthalmoscopy, optical coherence tomography and two-photon microscopy. By enabling the scientists to visualize different layers of the retina, these techniques allowed them to identify a small area of peak cone density and then estimate cone numbers by counting the cells in this unique area.

Based on their observations, the researchers found that cone densities reached more than 120,000 cells per square millimeter in a never-before-described fovea-like region of the area centralis—a density on par with that of primate foveas.

"There's no real landmark for this area like there is in humans," Aguirre said, "so to discover such a density was unexpected."

They also recognized that the "output side" of this cone-dense region corresponded with an area of dense , which transmit signals to the brain.

Human patients with macular degeneration experience a loss of photoreceptor cells—the rods and cones that process light—at or near the fovea, resulting in a devastating loss of central vision.

To see whether the fovea-like region was similarly affected in dogs, the Penn researchers used the same techniques they had employed to study normal dogs to examine animals that had mutations in two genes (BEST1 and RPGR) that can lead to macular degeneration in humans.

In both cases, the onset of disease affected the fovea-like region in dogs in a very similar way to how the diseases present in humans—with central retinal lesions appearing earlier than lesions in the peripheral retina.

"Why the fovea is susceptible to early disease expression for certain hereditary disorders and why it is spared under other conditions is not known," Cideciyan said. "Our findings, which show the canine equivalent of a human genetic disease affecting an area of the retina that is of extreme importance to human vision, are very promising from the human point of view. They could allow for translational research by allowing us to test treatments for human foveal and macular degenerative diseases in dogs."

In addition, the discovery offers insight into a rare human condition known as fovea plana, in which people have normal visual acuity but no "pit" in their fovea. In other words, their fovea resembles that of dogs, challenging the previously held assumption that lack of tissue and blood vessels overlaying the fovea is a prerequisite for the high resolution of vision.

The fact that dogs have a fovea-like area of dense may also indicate that dogs are seeing more acutely than once suspected.

"This gives us a structural basis to support the idea that dogs might have a higher visual acuity than has been measured so far," Beltran said. "It could even be the case that some breeds have an especially high density of cells and could be used as working for particular tasks that require high-level sight function."

Looking ahead, the researchers may focus on this fovea-like area in studies of therapies for not only X-linked retinal degeneration and Best disease but also other sight-related problems affecting the macula and fovea.

Explore further: Same cell death pathway involved in three forms of blindness

Related Stories

Same cell death pathway involved in three forms of blindness

January 16, 2014
Gene therapies developed by University of Pennsylvania School of Veterinary Medicine researchers have worked to correct different forms of blindness. While effective, the downside to these approaches to vision rescue is that ...

Team takes first step toward macular dystrophy gene therapy

October 15, 2013
Vitelliform macular dystrophy, also known as Best disease, is one of a group of vision-robbing conditions called bestrophinopathies that affect children and young adults. Caused by inherited mutations in the BEST1 gene, these ...

Newly developed chemical restores light perception to blind mice

February 19, 2014
Progressive degeneration of photoreceptors—the rods and cones of the eyes—causes blinding diseases such as retinitis pigmentosa and age-related macular degeneration. While there are currently no available treatments to ...

Gene therapy research cures retinitis pigmentosa in dogs

January 23, 2012
Members of a University of Pennsylvania research team have shown that they can prevent, or even reverse, a blinding retinal disease, X-linked Retinitis Pigmentosa, or XLRP, in dogs.

New twist in a blindness-causing disease gene found

September 21, 2011
After more than three decades of research, University of Pennsylvania veterinarians and vision-research scientists, with associates at Cornell University, have identified a gene responsible for a blindness-inducing disease ...

Recommended for you

Combination of type 2 diabetes and sleep apnoea indicates eyesight loss within four years

July 4, 2017
Research led by the University of Birmingham has discovered that patients who suffer from both Type 2 diabetes and obstructive sleep apnoea are at greater risk of developing a condition that leads to blindness within an average ...

Nearly 60% of pinkeye patients receive antibiotic eye drops, but they're seldom necessary

June 28, 2017
A new study suggests that most people with acute conjunctivitis, or pinkeye, are getting the wrong treatment.

Magnetic implants used to treat 'dancing eyes'

June 26, 2017
A research team has successfully used magnets implanted behind a person's eyes to treat nystagmus, a condition characterised by involuntary eye movements.

Drug shows promise against vision-robbing disease in seniors

June 21, 2017
An experimental drug is showing promise against an untreatable eye disease that blinds older adults—and intriguingly, it seems to work in patients who carry a particular gene flaw that fuels the damage to their vision.

Reproducing a retinal disease on a chip

June 15, 2017
Approximately 80% of all sensory input is received via the eyes, so suffering from chronic retinal diseases that lead to blindness causes a significant decrease in the quality of life (QOL). And because retinal diseases are ...

New gene therapy for vision loss proven safe in humans

May 16, 2017
In a small and preliminary clinical trial, Johns Hopkins researchers and their collaborators have shown that an experimental gene therapy that uses viruses to introduce a therapeutic gene into the eye is safe and that it ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.