Childhood Onset Strabismus: A Neurotrophic Factor Hypothesis

Rudell, Jolene C.; Filippi, Jérôme; Mustari, Michael J.; McLoon, Linda K.

doi:10.1080/2576117x.2021.1893585

Cited by 1 publication

(5 citation statements)

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“…The effects of neurotrophic factors on ocular motor neuronal function vary in development as well as in the maintenance and plasticity of the adult ocular motor system. 6 GDNF is present in EOMs, and the mRNA expression of GDNF is 26-fold higher in EOMs than that in other skeletal muscles. 8 Overexpression of GDNF by muscle greatly increased the number of motor axons innervating neuromuscular junctions in neonatal mice.…”

Section: Discussionmentioning

confidence: 87%

“… 14 The findings on neurotrophic factors also indicated its involvement in trophic signaling alterations in the EOMs, 20 which can trigger a microcascade of plasticity at the muscle and motor neuron levels. 6 It has been demonstrated that continuous treatment with a neurotrophic factor has the potential to correct eye alignment in a sustained manner, which may override compensatory mechanisms in the ocular motor system. 14 , 18 , 21 …”

Section: Discussionmentioning

confidence: 99%

“…They play a critical role in regulating the survival and development of both neurons and muscle fibers and can be transported in either anterograde or retrograde directions between neurons and EOMs. 6 EOMs express GDNF and IGF-1, and the expression levels of BDNF, NT-3, and NGF are higher compared with facial, buccinator, tongue, and limb muscles. 7 , 10 – 12 The effects of neurotrophic factors on EOM contraction profiles and patterns of innervation are diverse.…”

mentioning

confidence: 96%

“…Unlike incomitant esotropia, in which the underlying etiology can be attributed to paralysis of the ocular motor system, the underlying molecular and neurophysiological basis of concomitant esotropia is extremely complex and heterogeneous, influenced by genetic and environmental factors. 6 , 7 …”

mentioning

confidence: 99%

“… 8 Gene expression was found to be altered in strabismic human EOMs and tendons, 7 including the expression of neurotrophic factors that regulate the frequency and strength of muscle contractions by modulating the number of nerve fiber branches and the density of neuromuscular junctions. 9 Neurotrophic factors 6 , 10 are a family of proteins that are identified and produced in the neurons and muscles, including glial cell-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), neurotrophin-3 (NT-3), and nerve growth factor (NGF). They play a critical role in regulating the survival and development of both neurons and muscle fibers and can be transported in either anterograde or retrograde directions between neurons and EOMs.…”

mentioning

confidence: 99%

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Alteration of Neurotrophic Factors and Innervation in Extraocular Muscles of Individuals With Concomitant Esotropia

Hao,

Wang,

Liu

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose To determine whether neurotrophic factors and innervation in extraocular muscles (EOMs) were altered in different types of concomitant esotropia, and to explore the possible association between neurotrophic factors and innervation of EOMs in humans. Methods Patients with concomitant esotropia who required strabismus surgery were recruited from January to December 2022. Lateral rectus EOMs were obtained from patients, and controls were obtained from deceased organ donors. Immunofluorescence (IF) was performed to detect innervation of EOMs (neurofilament and synaptophysin), and immunohistochemistry (IHC) was used to detect the neurotrophic factors insulin-like growth factor-1 (IGF-1), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). The positive IHC results were further verified using western blotting (WB). One-way ANOVA followed by a Dunnett's multiple comparison post hoc test was used for continuous variables and the χ 2 test for categorical variables. Spearman correlation analysis was used for the correlation analysis. Results We collected lateral rectus EOM samples from acute and chronic types of concomitant esotropia and controls. Consistent with IHC, WB showed that IGF-1 was significantly increased in patients with acute acquired comitant esotropia or essential infantile esotropia compared with controls. In IF, synaptophysins were significantly increased only in acute acquired comitant esotropia compared with controls. Furthermore, Spearman correlation analysis showed that the correlation between IGF-1 and synaptophysin was borderline ( P = 0.057) for patients with acute acquired comitant esotropia. Conclusions Our study highlights the role of IGF-1 and altered innervation of EOMs in acute acquired comitant esotropia, suggesting that an effect of increased IGF-1 on nerve innervation may temporarily cause a compensatory increase in the strength of lateral rectus muscles.

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Section: Discussionmentioning

confidence: 87%