Childhood Onset Strabismus: A Neurotrophic Factor Hypothesis

Abstract

ABSTRACT Strabismus is a genetically heterogeneous disorder with complex molecular and neurophysiological causes. Evidence in the literature suggests a strong role for motor innervation in the etiology of strabismus, which connects central neural processes to the peripheral extraocular muscles. Current treatments of strabismus through surgery show that an inherent sensorimotor plasticity in the ocular motor system decreases the effectiveness of treatment, often driving eye alignment back toward its misaligned pre-surgical state by altering extraocular muscle tonus. There is recent interest in capitalizing on existing biological processes in extraocular muscles to overcome these compensatory mechanisms. Neurotrophins are trophic factors that regulate survival and development in neurons and muscle, including extraocular muscles. Local administration of neurotrophins to extraocular muscles partially reversed strabismus in an animal model of strabismus. The hypothesis is that sustained release of neurotrophins gives more time for the ocular motor system to adapt to a slow change in alignment in the desired direction. The effect of neurotrophins on extraocular muscles is complex, as different neurotrophic factors have diverse effects on extraocular muscle contraction profiles, patterns of innervation, and density of extraocular muscle precursor cells. Neurotrophic factors show promise as a therapeutic option for strabismus, which may help to improve treatment outcomes and offset devastating amblyopia and psychosocial effects of disease in strabismus patients.