Cystathionine β-synthase deficiency impairs vision in the fruit fly, Drosophila melanogaster

Abstract

PurposeIn humans, deficiency in Cystathionine {beta}-Synthase (CBS) levels leads to an abnormal accumulation of homocysteine and results in classic homocystinuria, a multi-systemic disorder affecting connective tissue, muscles, the central nervous system and the eyes. However, the genetic and molecular mechanisms underlying vision problems in patients with homocystinuria are little understood. Materials and MethodsThe fruit fly, Drosophila melanogaster, is a useful experimental system to investigate the genetic basis of several human diseases, but no study to date has used Drosophila as model of homocystinuria. Here we use genetic tools to down-regulate CBS and classical behavioral assays to propose Drosophila as a model of homocystinuria to study vision problems. ResultsWe present evidence that CBS-deficient flies show an abnormal stereotypical behavior of attraction towards a luminous source or phototaxis, consistent with severe myopia in humans. We show that this behavior cannot be fully attributed to a motor or olfactory deficiency but most likely to an impaired vision. CBS-deficient flies are overall smaller, but smaller eyes do not explain their erratic phototactic response. ConclusionsWe propose Drosophila as a useful model to investigate ocular manifestations underlying homocystinuria.