Abstract
Purpose :
Infantile nystagmus syndrome (INS) is characterized by involuntary oscillatory eye movements, beginning in infancy. Eye muscle specimens from patients with INS display an increased proportion of slow myosin heavy chain (MyHC) positive muscle fibers and alterations in the neuromuscular junction. It is unknown if these changes are the cause or effect of long-standing nystagmus. Using albino mice as a model of infantile nystagmus, we examined the development of extraocular muscles and their innervating motor neurons during postnatal development.
Methods :
We examined the extraocular muscles of postnatal day (P) 0, P10, P14, P21, 6 and 12 week old albino mice and littermate wild-type controls. Balc/c albino mice were crossed to mixed background pigmented mice, and heterozygous mice were crossed to generate experimental litters. Using immunostaining, we compared slow and fast myosin heavy chain (MyHC) composition between control and albino mice extraocular muscles (EOMs) (n=3-6 animals of each genotype at each timepoint). Data were analyzed using unpaired student’s t-test.
Results :
In control animals, there is a higher proportion of slow MyHC fibers at P0 (5.28±0.53%), with decreasing expression over time (1.37± 0.12% at 12 weeks), consistent with prior reports. In albino mice, the proportion of slow MyHC fibers is similar to controls at P0 (4.84±1.48%), P10 (4.88±3.14%), and P14 (1.04±0.06%). By P21, there is a higher proportion of slow MyHC fibers in albinos (2.52±0.31%) compared to controls (1.23±0.082%), which persists into adulthood (4.22±1.27% slow MyHC fibers in albinos, 1.37± 0.12% in controls at 12 weeks).
Conclusions :
Albino mice, who display nystagmus, have an increase in the proportion of slow MyHC fibers in their extraocular muscles. This is similar to the findings seen in human samples. We see evidence of this difference as early as P21, but not before eye opening (~P12), suggesting that there may be sensory activity-dependent mechanisms that contribute to EOM development.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.