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Age-dependent regional retinal nerve fibre changes in SIX1/SIX6 polymorphism.

Jason Charng1, Mark Simcoe2, Paul G Sanfilippo1,3

  • 1Centre for Ophthalmology and Visual Science (incorporating Lions Eye Institute), The University of Western Australia, 2 Verdun St, Perth, WA, 6009, Australia.

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|July 29, 2020
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Summary

Genetic variants in SIX1/SIX6 influence glaucoma risk. While linked to thinner retinal nerve fiber layer (RNFL) in older adults, these SIX1/SIX6 gene variants show no effect in younger individuals.

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Area of Science:

  • Ophthalmology
  • Genetics
  • Neuroscience

Background:

  • Polymorphisms in SIX1/SIX6 are associated with glaucoma.
  • Previous studies indicate that SIX1/SIX6 risk alleles correlate with reduced retinal nerve fiber layer (RNFL) thickness in older adults.

Purpose of the Study:

  • To investigate whether SIX1/SIX6 genetic variants affect RNFL thickness in younger individuals.
  • To compare the impact of SIX1/SIX6 variants on RNFL thickness between young and older adult cohorts.

Main Methods:

  • Comparison of RNFL thickness in healthy young adults (mean age 20) and older adults (mean age 63) of Northern European descent.
  • Analysis of SIX1 (rs10483727) and SIX6 (rs33912345) polymorphisms and their association with RNFL thickness in different ocular sectors.

Main Results:

  • No significant association was found between SIX1/SIX6 risk alleles and RNFL thinning in younger individuals.
  • In older adults, SIX1 and SIX6 risk alleles were associated with thicker RNFL in the nasal sector.
  • In the temporal sector of older adults, the SIX6 risk allele (rs33912345) was linked to thinner RNFL, with a similar trend for the SIX1 variant (rs10483727).

Conclusions:

  • The influence of SIX1/SIX6 gene variants on RNFL thickness appears to manifest later in adult life.
  • Age is a critical factor in the manifestation of SIX1/SIX6 genetic effects on retinal structure.