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Discovery by UPenn Team Gives Insight into Blinding Retinal Diseases and Hope for Better Understanding and Treatment of Macular Degeneration.

Posted by Tom Cockley | Posted on April 15, 2014

In humans, the fovea, in the center of the retina, is critically important to viewing fine details.  According to new research, although some animals have a similar feature in their eyes, researchers believed 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.  Significantly, this retinal region is susceptible to genetic blinding diseases such as macular degeneration (AMD) in dogs just as it is in humans.

New discovery a surprise to ophthalmic researchers

“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.

The research was published in the journal PLOS ONE

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 region of increased cell density. In the new study from the University of Pennsylvania, 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.

UPenn researchers find cone densities in dogs similar to humans

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 within the dogs’ area centralis — a density on par with that of primate foveas.

Human patients with macular degeneration (AMD) 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 examined animals that had mutations in two genes (BEST1 and RPGR) that can lead to macular degeneration in humans.

New discovery opens doors to more research in what causes human AMD

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.

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

Large non-primate animals have become increasingly attractive to assess efficacy and safety of a variety of treatment modalities that are being considered for clinical trials in human patients. Dogs, by far, have the widest array of naturally occurring inherited retinal degenerations with >18 causative genes identified to date. Previously it was thought that the lack of a foveo-macular region in the canine retina would limit its use for studies aimed at understanding the pathogenesis of macular degeneration and its treatments. But these current results describing a canine retinal area with primate fovea-like cone density, and a predilection in two canine models for early disease within this area, similar to human patients, sets the stage for better understanding of the susceptibility of this region to molecularly specific insults and evaluation of potential treatments for human macular degenerations.

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 Tom Cockley is president of Gulden Ophthalmics and is the third generation of the nearly 75-year-old visionary company that brings innovative, time-saving, utilitarian products to vision and health care professionals.

 

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