Increased PRSS56 expression is a causal factor and therapeutic target for human axial high myopia - PubMed
4 hours ago
- #Axial High Myopia
- #Therapeutic Target
- #PRSS56
- High myopia (HM) is characterized by ocular axial elongation and is often inherited, with many causative genes unknown.
- Study refined the MYP12 locus on 2q37.1 to a 3.9-Mb region and identified noncoding promoter variants (c.-187G>T and c.-187G>C) in PRSS56 in HM pedigrees.
- Increased PRSS56 expression was found in patient-derived iPSCs and knock-in mice, correlating with myopia phenotypes.
- Noncoding variants promote PRSS56 self-expression via enhanced binding to transcription factor EGR1.
- Higher PRSS56 levels directly increase ocular axial length in a dose- and activity-dependent manner in transgenic mice.
- Guinea pig myopia models showed high Prss56 expression; short-wave light exposure reduced Prss56 levels and attenuated axial elongation.
- Mechanistically, higher PRSS56 expression is linked to reduced myosin-4 in sclera and scleral remodeling signatures, correlating with axial elongation.
- Results provide genetic and functional evidence for PRSS56 variants' pathogenic role in HM and highlight PRSS56 as a therapeutic target for juvenile HM.