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Advancing laminitis research — a collaborative effort
Institute at Penn Vet conducting studies, sharing research with colleagues internationally


DVM360 MAGAZINE


The first of Pollitt's two models of inducing horses with laminitis is feeding oligofructose, a commercially available, natural carbohydrate, similar to the carbohydrate derived from many temperate grasses.


Figure 1: Normal anatomy of the distal phalanx/coffin bone and related structures in the equine foot. (Figures: Molly Higgins/University of Pennsylvania School of Veterinary Medicine)
"Once you dose the oligofructose into the horse, it changes the microflora of the hindgut dramatically and very rapidly," says Pollitt. This produces an overgrowth of Streptococcus equinus complex, a gram-positive bloom in the hindgut. This makes a horse moderately ill and initiates the beginning stages of the disease at the basement membrane of the lamellae in the hoof.

"The (institute's) plan is to repeat that model, but at much earlier time points," Pollitt explains. "We want to track back to the very earliest molecular events that are occurring to give us an insight into how soon this bloom of microbes in the hindgut affects the lamellae of the feet."

Institute researchers have good evidence that as early as 12 hours post-dosing, significant changes occur in the lamellar basement membrane. They will use the in vivo model, collecting samples of tissue from the basement membrane as early as six hours, 12, 18 and 24 hours post-dosing.

There is no need to produce end-stage laminitis per se; the horses barely notice the effect of the induction and effects of the oligofructose in their hindgut.

"At this time we know plenty about the eventual disease. Our goal now is to study the very early induction phases, and ethically this is preferable," Pollitt says.


Figure 2: Rotation of the distal phalanx/coffin bone due to the compromised bond between the epidermal and dermal lamellę tissue along the front of the foot.
The samples will going to a leading equine genomics expert, Bhanu Chowdhary, BVSc & AH, MVSc, PhD, professor in the Department of Veterinary Integrative Biosciences at Texas A&M University, who will perform a genomic analysis with the full equine genome micro array. "This is a major advantage of the laminitis institute," says Pollitt. "We have a researcher consortium around the world, from Australia, to Texas, to Penn Vet."

Galantino-Homer's lab will be doing a proteomic analysis of the blood and tissues from the horses at the early time points to note the early events.

Pollitt's other model is a hyperinsulinemic model, working with Standardbred horses. Insulin is dramatically laminitogenic. Researchers can induce laminitis in Standardbred horses as soon as 48 hours by making them hyperinsulinemic while keeping their glucose levels normal, using a euglycemic-hyperinsulinemic clamp extended to 48 hours. "It's quite difficult to do," says Pollitt, "but it provides quite dramatic results."


Figure 3: Sinking of the distal phalanx caused by complete loss of the bond between the epidermal and dermal lamellę tissue.
The Grayson research involves gene expression and proteomics (study of component proteins) to note expression differences between the control and the induced horses to try to fill some gaps in the pathogenesis.

"In that effort we are working with our epithelial stem-cell colleagues on ways to culture the basal cells, the epidermal lamellar cells that are right at the interface with the basement membrane," says Galantino-Homer.

"We assume that those cells are going to be at ground zero, regardless of the initiating cause of laminitis."

Whether it's the case of these cells proliferating when they're not supposed to be, releasing proteases that break down the basement membrane, being affected by inflammation or responding to proposed laminitis trigger factors, those are the cells of interest.

If funding allows, the institute would like to try to develop biomarkers to help identify horses at risk for laminitis.


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Source: DVM360 MAGAZINE,
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