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Linda K McLoon, Christy L Willoughby, Jérome Fleuriet, Mark M G Walton, Michael J. Mustari; Controlling Eye Alignment Development with Glial Derived Neurotrophic Factor. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.
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© ARVO (1962-2015); The Authors (2016-present)
Many forms of childhood onset strabismus are of unknown etiology. One potential neurotrophic factor involved in controlling normal oculomotor development is glial derived neurotrophic factor (GDNF). We tested the hypothesis that sustained GDNF treatment of a single extraocular muscle in infant monkeys would produce a strabismus.
One medial rectus muscle in each of 3 infant monkeys was implanted with pellets containing GDNF that provided sustained release of 2 μg/day for 3 months. Eye alignment was monitored weekly. At the end of 3 months, the extraocular muscles from the treated infants and age-matched controls were examined morphometrically for mean cross-sectional areas and neuromuscular junction size and density.
At the end of 3 months, all three monkeys were strabismic. Two patterns of changes in eye alignment were evident. One infant’s eyes moved from exotropic at birth toward normal alignment at 1 and 2 months; however, over the course of the final month alignment became significantly exotropic. The 2 other monkeys showed a slow decrease in their exotropia in the first month, but stabilized at approximately 10 degrees of misalignment. Analysis of the muscles revealed that GDNF treatment resulted in significantly increased mean myofiber cross-sectional areas. There were increased numbers of neuromuscular junctions in the GDNF-treated eye muscles, and the morphology was markedly different from that of age-matched control infant monkeys. The neuromuscular junctions were less complex but more widely distributed.
Similar to sustained treatment with insulin growth factor-1, sustained unilateral treatment with GDNF of a single extraocular muscle in infant monkeys resulted in animals that were strabismic. There were significant alterations in innervational patterns in the treated muscles. GDNF has been shown to increase neuromuscular junction dynamic remodeling, as well as increase synaptic activity. Thus, we suggest that altered GDNF signaling may be involved in the development of strabismus in otherwise normal infants.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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