Icelandic horses

VGL research sheds light into potential genetic risk factors for equine recurrent uveitis (ERU) in the Icelandic horse!

The study is the first to investigate potential risk factors for equine recurrent uveitis in the Icelandic horse and sheds light into the genetic factors behind disease development in the breed.

Equine recurrent uveitis (ERU) is the leading cause of blindness in horses and there are several breeds where a genetic basis is suspected, the Icelandic horse among them. ERU is characterized by either repeated episodes of inflammation or continuous low levels of inflammation of the uveal tract (middle layer of the eye). This inflammation causes cumulative damage to the ocular tissue, which can lead to blindness.

An international study led by VGL director, Dr. Rebecca Bellone, in collaboration with Dr. Michala de Linde Henriksen, from Colorado State University, and VGL research intern and second year UC Davis veterinary student, Yael (Izzie) Hack, among others, aimed to identify risk factors associated with ERU in the Icelandic breed by studying several factors in 11 ERU affected horses and 45 healthy controls.

Reflecting on what led her to pursue this study, Dr. Henriksen explains:

 I’m originally from Denmark where the Icelandic horse is very popular. I saw a lot of Icelandic horses with ERU as a student and intern at University of Copenhagen and have always wanted to further investigate this breed. I teamed up with Dr. Tina Pihl, who is a large animal internist from University of Copenhagen, to investigate ophthalmic diseases with focus on ERU in the Icelandic horse. During our initial prevalence study, given her expertise with inherited ocular disorders, we contacted Dr. Rebecca Bellone to collaborate on the genetic aspect of this study. It has been such a pleasure to work with Dr. Bellone, Izzie Hack, and other members of the VGL research team.”

In this study, serum titers for Leptospira interrogans (implicated as the inciting cause in other horses) as well as a mutation in the premalanosome protein (PMEL) gene, which causes the silver coat color dilution and another ocular disorder in the Icelandic horse (multiple congenital ocular anomalie), were investigated as risk factors. However, neither Leptospira interrogans or the PMEL mutation were associated with ERU in the present study.

A genome-wide association study (GWAS) was then performed to identify genetic markers associated with ERU, and a variant on horse chromosome 11 was found to be associated. This variant is in a promising candidate gene for ERU, specifically the tissue inhibitor of metalloproteinase (TIMP2) gene. Other studies have shown reduced expression of the TIMP2 protein as well as decreased enzymatic activity of TIMP2 in uveitis cases when compared to healthy control samples. Moreover, expression of TIMP2 in the retina was also greatly reduced in horses with ERU.

Initial exploration of the TIMP2 gene in this study population failed to reveal causative mutations in the coding region of the gene, indicating the need for further exploration of regulatory the regions that may impact gene expression. Dr. Bellone notes

These findings support a genetic basis for ERU in Icelandic horses and justification for further investigation to identify causal predisposing factors for ERU in this breed. We are currently working to recruit additional samples to replicate these findings and further interrogate TIMP2. “

For more information about the study, read the full publication here.

To hear about the student’s experience with research, check out our “Meet the Scientist” side bar with second year UC Davis Veterinary Student Izzie Hack.