Identification of key factors regulating healing and adaptation processes of EOMs triggered by strabismus surgery

SNIC 2017/7-210


SNAC Small

Principal Investigator:

Fatima Pedrosa-Domellöf


Umeå universitet

Start Date:


End Date:


Primary Classification:

30108: Cell and Molecular Biology




he extraocular muscles (EOMs) are the effectors for ocular motility and disturbed eye movement co-ordination leads to ocular misalignment, also known as strabismus, affecting approximately 5% of the population. The treatment of strabismus often requires surgery on the EOMs. However, the outcome of strabismus surgery is often unsatisfactory, with reoperation rates ranging anywhere from 25% to 69% due to initial under- or overcorrection and to relapse. At this moment, the contributors to this relapse are still unknown. The EOMs are classified as a separate muscle type given their distinct properties from other muscles in a physiological state and the pathological context of muscular dystrophies. The gene expression profile of the EOMs differs fundamentally from that of the limb muscles with respect to metabolic pathways, structural components, developmental and regeneration markers, by over 300 genes. However, there is no knowledge about the importance of different genes and, furthermore, whether differential gene expression could exist in different cell populations of EOMs. The study of the molecular portfolio of EOMS at distinct time points after strabismus surgery could give us insights about specific process triggered by this surgical procedure. This project is part of a larger study using an animal model of strabismus surgery and patient material with the aim of understanding how the unusual molecular composition of the EOMs may contribute to their response to strabismus surgery. Our animal model consists of a set of 20 male rabbits that have been subjected to shortening (resection) of the rectus superior muscle, one of the strabismus surgery procedures applied in human patients. The EOMs of the rabbits have been collected after 1, 2, 4 or 6 weeks after surgery in order to study the time line of the changes occurring after the surgery. A control group of non-operated rabbits has been also included in the study. Total RNA has been isolated from the EOMs and applying Next Generation Sequencing (RNA-sequencing) we aim to investigate the adaptations that occur in the operated EOM leading to restoration of muscle length, and thereby to failure of strabismus surgery. Data derived from RNA sequencing will provide valuable information concerning the mechanistic and adaptive strategies that have evolved to meet the highly specialized functional requirements of EOMs. The data obtained in this study will be correlated with a large collection of patient material and with changes at the whole muscle level studied by magnetic resonance imaging (MRI). This is the basis for future modifications of surgical procedures or for completing them with pharmaceutical agents. At the clinical level, the high rate of strabismus surgery failure over time is a problem that affects a significant number of patients, with implications for their working and driving capacities, morbidity related to the fact that a new surgical intervention is required and with significant costs for society. Finding new ways to improve the overall success rate of strabismus surgery is crucial, as it is clear that efforts made with respect to the surgical procedures themselves, alone, are not sufficient.