Equine veterinarians make steps toward solving the laminitis mystery - DVM
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Equine veterinarians make steps toward solving the laminitis mystery
An intensive area of study, laminitis still confounds researchers looking to advance our knowledge of disease origin, prevention and treatment. But some promising new research projects are looking to make great strides toward better understanding.


They've been working with epithelial stem cell biologist Makoto Senoo, PhD, at the University of Pennsylvania's Department of Biology, to adapt the epithelial stem cell selective and "organotypic culture systems" used in human medicine to generate skin and eye cornea tissue grafts for transplantation and research studies. "This will allow us to investigate the effects of environmental factors associated with the development of laminitis, such as inflammatory mediators or supraphysiologic insulin levels, on the ability of lamellar cells to remain viable, maintain cell-matrix and cell-cell adhesions and maintain their normal gene and protein expression patterns," says Galantino-Homer.

"The major part of our work has been looking at the molecular studies, the pathophysiology of laminitis using large-scale quantitative analysis of protein expression and gene expression," Galantino-Homer explains. "We are so indebted to the horse genome project, which has allowed me to do the kind of work that we and other equine disease researchers are doing. We're taking samples from the model systems and using the most current quantitative proteomics methods and analysis relative to the published equine genome sequence to identify and quantify all of the proteins that are present within a certain range of protein sizes.

"If I had tried to do that prior to the release of the annotated horse genome sequence, my results would have been without value," she continues. "Whereas now I'm able to match those protein sequences to the published horse genome sequence and predict protein and gene identities. Compared to previous gene and protein expression studies based on selected targets, the global high-throughput approaches that are now available to us are rapidly accelerating equine disease research progress. The equine genome has also allowed us and other researchers to use new technologies for large-scale 'transcriptomics' to investigate global gene expression patterns. We are now getting a more complete picture of the gene and protein players in laminitis pathogenesis."

An ongoing collaboration with Samantha Brooks, PhD, at Cornell University's Department of Animal Science, is using next-generation high-throughput RNA-sequencing to investigate global changes in gene expression in laminitic horses and to use the information generated to refine genome annotation of hoof-specific gene expression.

The focus of Galantino-Homer's work is to improve our understanding of laminitis pathophysiology with the overall goal of making laminitis easier to diagnose, prevent and treat. "One of our major goals is to discover diagnostic serum biomarkers," she says. "The Grayson-Jockey Club Research Foundation recently funded our serum biomarker studies with Dr. Julie Engiles from the University of Pennsylvania and Dr. Bettina Wagner from Cornell. Target diagnostic proteins have been selected based on our previous GJCRF-funded proteomics studies and will be investigated in experimental and naturally occurring laminitis cases from the Laminitis Discovery Database.

"However, it's unlikely that there will be a single biomarker that is specific for laminitis due to the overlap with other inflammatory diseases and musculoskeletal injury," she continues. "Fortunately, the technology is now in place for multiplex assays that allow the simultaneous evaluation of multiple factors using a single serum sample. We've been working with Dr. Wagner, the director of Automated Serology/Immunology at Cornell's Animal Health Diagnostic Center to develop these assays. We're hoping to find a specific signature that we can use to monitor the at-risk cases, also in regard to aggressive intervention and eventual prognosis."

Looking to the future

As we reflect on the progress during the past 10 years, we find more pieces of the laminitis puzzle that are inextricably linked. The overriding feeling is that of accomplishment in getting closer to solving the mystery. This is because of the dedication of many trailblazers, veterinarians, farriers, researchers, owners and caregivers who continually advance the understanding, prevention and treatment of laminitis. As a profession and industry, we stand on the shoulders of all these achievements. This ground work positions other researchers and collaborators on the launching pad for even greater future accomplishments as we approach 2020 and the goal of conquering laminitis.

Ed Kane, PhD, is a researcher and consultant in animal nutrition. He is an author and editor on nutrition, physiology and veterinary medicine with a background in horses, pets and livestock. Kane is based in Seattle.


Source: DVM360 MAGAZINE,
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