We have shown a reduction in eye size and in the volume of the optic nerve upon MO knockdown of zebrafish six6a, and we were able to rescue these phenotypes with co-injection of the human SIX6 non-risk allele, demonstrating that the zebrafish six6a gene is the likely functional ortholog to human SIX6. We identified five alleles that could not rescue the small eye and optic nerve phenotypes, and we observed a reduction in retinal nerve fiber layer thickness in POAG patients homozygous for the His141 SIX6 risk allele. The gene discussed is SIX6; the disease is open-angle glaucoma.