Metabolic and neuroactivity imbalances in plasma from aniridia patients with PAX6 haploinsufficiency

PAX6 is a transcription factor crucial for the development of the eye, pancreas, and brain. Heterozygous variants resulting in PAX6 haploinsufficiency are the main genetic cause of congenital aniridia, characterized by both anterior and posterior ocular defects and sight loss. The extra-ocular features of PAX6 haploinsufficiency are becoming more widely recognised, with systemic manifestations like obesity, diabetes, and neurological/behavioural disorders being reported. In this study, we uncovered the metabolomic profile of the blood plasma from 25 PAX6-related aniridia patients compared to gender and age-matched controls. We found significant disruptions in lipid and energy metabolism, increased oxidative stress and neurotransmitters imbalances, as well as alterations linked to the gut microbiome. This study identified novel metabolic changes associated with PAX6 haploinsufficiency, providing evidence for the systemic aetiology of congenital aniridia and emphasizing the need for multidisciplinary management and further exploration into ocular and systemic therapeutic approaches.