A complex interplay of several dysregulated mechanisms related to the immune system appears responsible for the development of equine recurrent uveitis (ERU), according to the authors of a review.
The immune-mediated disease affects the eyes of horses around the world, ultimately leading to blindness. It is characterized by painful, inflammatory bouts alternating with periods of quiescence (causing no trouble or symptoms).
During the course of the disease, both eyes can eventually be affected and, since blind horses pose a threat to themselves and their surroundings, affected animals are often euthanized.
Roxane Degroote and Cornelia Deeg, in their review published in the journal Frontiers in Immunology, noted that ERU shows strong clinical and pathological resemblance to autoimmune uveitis in humans.
The exact cause of the onset of ERU is so far unclear, they said. T cells – one of the important white blood cells of the immune system and a key player in the adaptive immune response – are believed to play a main role in the development of the disease.
The T cells overcome the blood-retinal barrier to invade the eye, which is physiologically devoid of peripheral immune cells. These cells cause severe inflammation within the eye, especially in their primary target, the retina.
Increasing numbers of immune cells invade and accumulate in the eye with every inflammatory attack, gradually destroying the retina. With every inflammatory episode, retinal degeneration increases until eyesight is completely lost.
Prevalence among horses is high, ranging from 2% to 25% in the US and 8% to 10% in Europe.
In ERU, T cells show enhanced deformability and migration ability, they said, which is reflected in the composition of their proteome and downstream interaction pathways, even in the quiescent stage of the disease. The protein changes so far identified mainly have a role in cell adhesion, cell migration and regulation of cell shape.
Besides the dysregulation of adaptive immune cells, emerging evidence suggests that cells of the innate immune system may also directly contribute to ERU pathogenesis, the pair said.
Degroote and Deeg, both with the Faculty of Veterinary Medicine at Ludwig-Maximilians-University in Munich, set out in their review to examine the growing body of immunological evidence in cases of ERU. The pair traversed the role of the adaptive immune system and the innate immune system in the disease.
Overall, the immunological evidence points to a complex interplay of several dysregulated mechanisms in the development of the disease, they said.
On the one hand, these can be linked to changes in components of the immune system, such as deviant functional T cells, latently activated granulocytes (another type of white blood cell that fights infection) and involvement of the various immune mechanisms to fight infection.
“On the other hand, this dysregulation points to a pivotal pro-inflammatory role of retinal cells with critically impaired function in the target organ itself.”
Degroote and Deeg said the interaction of these dysfunctional molecular mechanisms driving ERU, as well as their exact individual role and timing in the development of the disease, warrants further assessment.
The possibility of involvement of the commensal microbiota – the wide range of microorganisms that collectively inhabit the horse – also needs to be addressed, they said.
Degroote RL and Deeg CA (2021) Immunological Insights in Equine Recurrent Uveitis. Front. Immunol. 11:609855. doi: 10.3389/fimmu.2020.609855