Jennifer K. Brueckner

Extraocular muscles: basic and clinical aspects of structure and function

Although extraocular muscle is perhaps the least understood component of the oculomotor system, these muscles represent the most common site of surgical intervention in the treatment of strabismus and other ocular motility disorders. This review synthesizes information derived from both basic and clinical studies in order to develop a better understanding of how these muscles may respond to surgical or pharmacological interventions and in disease states. In addition, a detailed knowledge of the structural and functional properties of extraocular muscle, that would allow some degree of prediction of the adaptive responses of these muscles, is vital as a basis to guide the development of new treatments for eye movement disorders.

Spatial and temporal patterns of myosin heavy chain expression in developing rat extraocular muscle

SummaryThe present study describes transitions in myosin heavy chain expression in the extraocular muscles of rats between the ages of E17 and adult. The unique phenotype of the extraocular muscle is reflected in its fibre type composition, which is comprised by six distinct profiles, each defined by location (orbital versus global layer) and innervation pattern (single versus multiple terminals). During extraocular muscle myogenesis, developmental myosin heavy chains were expressed in both primary and secondary fibres from embryonic day E17 through the first postnatal week. At this time, the downregulation of developmental myosin heavy chain isoforms began in the global layer in a fibre type-specific manner, reaching completion only after the first postnatal month. By contrast, developmental isoforms were retained in the overwhelming majority of orbital layer fibres into adulthood and expressed differentially along the length of these fibres. Fast myosin heavy chain was detected pre- and postnatally in developing secondary fibres and in all of the singly innervated fibre types and one of the multiply innervated fibre types in the adult. As many as four fast isoforms were detected in maturing extraocular muscle, including the extraocular muscle-specific myosin heavy chain. Slow myosin heavy chain was expressed in primary fibres throughout development and in one of the multiply innervated fibre types in the adult. In contrast, the pure fast-twitch retractor bulbi initially expressed slow myosin heavy chain in fibres destined to switch to the fast myosin heavy chain developmental programme. Based upon spatial and temporal patterns of myosin heavy chain isoform transitions, we suggest that epigenetic influences, rather than purely myogenic stage-specific factors, are critical in determining the unique extraocular muscle phenotype.

A “Second Life” for gross anatomy: Applications for multiuser virtual environments in teaching the anatomical sciences

This article describes the emerging role of educational multiuser virtual environments, specifically Second Life™, in anatomical sciences education. Virtual worlds promote inquiry‐based learning and conceptual understanding, potentially making them applicable for teaching and learning gross anatomy. A short introduction to Second Life as an anatomical educational tool is provided, along with description of existing anatomy applications and future directions for this innovative teaching modality. Anat Sci Educ.

Vestibulo-ocular pathways modulate extraocular muscle myosin expression patterns

Abstract The genetic and epigenetic influences that establish and maintain the unique phenotype of the extraocular muscles (EOMs) are poorly understood. The vestibulo-ocular reflex (VOR) represents an important input into the EOMs, as it stabilizes eye position relative to the environment and provides a platform for function of all other eye movement systems. A role for vestibular cues in shaping EOM maturation was assessed in these studies using the ototoxic nitrile compound 3’,3’-iminodipropionitrile (IDPN) to eliminate the receptor hair cells that drive the vestibulo-ocular reflex. Intraperitoneal injections of IDPN were followed by a 2-week survival period, after which myosin heavy chain (MyHC) analysis of the EOMs was performed. When IDPN was administered to juvenile rats, the proportion of eye muscle fibers expressing developmental and fast myosins was increased, while EOM-specific MyHC mRNA levels were downregulated. By contrast, IDPN treatment in adult rats affected only the proportion of fibers expressing developmental MyHC isoforms, leaving the EOM-specific MyHC mRNA unaltered. These data provide evidence that the VOR modulates EOM-specific MyHC expression in development. The lack of significant changes in EOM-specific MyHC expression in adult EOM following IDPN administration suggests that there may be a critical period during development when alterations in vestibular activity have significant and permanent consequences for the eye muscles.

The oculomotor periphery: the clinician's focus is no longer a basic science stepchild

The study of the oculomotor periphery, the extraocular muscles and their orbital attachments, is undergoing a rapid expansion. This is an important progression for both basic and clinical communities as, for too long, the ophthalmologist has worked primarily in the periphery and the basic researcher has been occupied with study of the central components of the oculomotor system. From recent studies, it is clear that the morphology, cell and molecular biology, and genetics of the eye muscles and their corresponding motoneuron pools, and muscle attachments within the orbit are more complex than has heretofore been appreciated.

Types and time course of the alterations induced in monkey blink movements by botulinum toxin

The alterations induced in eyelid movement metrics subsequent to unilateral injections of botulinum toxin type A into the orbicularis oculi muscle were studied in chronic alert monkeys using the search coil technique. Botulinum toxin caused rapid paralysis of blinks in the treated eyelid. The amplitude and peak velocity of blinks generated by this eyelid remained at or below 20% of that of the fellow, untreated eyelid for 10–20 days. Blink amplitude gain increased linearly thereafter, attaining control values by 40–60 days after injection. Recovery of blink peak velocity was slower. The adaptive alterations in blink duration that were observed during the acute phase of toxin paralysis suggest that the mechanisms responsible for blink reflex plasticity may produce bilateral adjustments in eyelid function. Taken together, these data establish a quantitative data base that can be exploited in order to: (1) better understand the neural adaptive mechanisms that operate during eyelid movements and (2) allow quantitative comparisons between current treatment protocols that employ botulinum toxin and protocols that may lead to improvements in the treatment of chronic eyelid spasm (blepharospasm).

The Neuronal Voltage-Gated Sodium Channel, Scn8a, Is Essential for Postnatal Maturation of Spinal, but Not Oculomotor, Motor Units

Mice with a nontargeted transgene insertion at the motor endplate disease (med) locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a. We characterized severe skeletal muscle atrophy beginning by Postnatal Day 10 (P10) and death by P20 in the med(tg) mouse. Denervation was functional, rather than structural, since the Scn8a mutation was not accompanied by retraction of neuromuscular contacts, motoneuron death, or decreased motoneuron soma diameter. Although pathology consistent with denervation was seen in both hindlimb and forelimb musculature, the postnatal maturation of the extraocular muscles was not altered. The onset of paralysis is likely coincident with the time that the Scn8a sodium channel normally assumes a critical role in the initiation and/or propagation of action potentials in spinal motoneurons. By contrast, the lack of consequences for extraocular muscle suggests that the Scn8a voltage-gated sodium channel may be of relatively minor importance for oculomotor motoneurons.

Unilateral Double Plantaris Muscle: A Rare Anatomical Variation

Un segundo musculo plantar unilateral fue descubierto durante una diseccion anatomica de rutina, en una mujer de 47 anos de edad con Enfermedad de Huntington Chorea. En la cara medial de la piena derecha, el cadaver presentaba, bilateralmente, el musculo plantar y un musculo anomalo, morfologicamente distinto, que se asemejaba a un segundo musculo plantar. Los vientres medial y lateral del musculo plantar anomalo se originaban del condilo medial del femur y formaban un tendon corto que se fusionaba con el tendon del musculo plantar lateral.

Students' responses to the introduction of a digital laboratory guide in medical neuroscience

This study investigated student acceptance of a digital laboratory guide in a medical neuroscience course. The guide was created in Macromedia™ Authorware 5.2 by transforming a text-based lab manual into a comprehensive multimedia program. Student attitudinal survey data indicated that the guide was used primarily as a study tool at home. Some 53% of students (primarily males) used the guide for independent study exclusively, while the remainder used it for both independent and group study; 87% of the class used the guide as a routine study tool rather than as a final review for examinations. Most students perceived that the guide increased their study efficiency and lab performance while decreasing their out-of-class study time in the lab. Female students were significantly more enthusiastic about the guides impact on their study efficiency, lab performance and laboratory study time. Gender differences in student satisfaction with and use of instructional multimedia are discussed.