Cystathionine β-synthase Deficiency Impairs Vision in the Fruit Fly, Drosophila melanogaster

ABSTRACT

Purpose

Deficiency in Cystathionine β-synthase (CBS) leads to an abnormal accumulation of homocysteine and results in classical homocystinuria, a multi-systemic disorder that affects connective tissue, muscles, the central nervous system, and the eyes. However, the genetic players and mechanisms underlying vision alterations in patients with homocystinuria are little understood.

Materials and Methods

The fruit fly, Drosophila melanogaster, is a useful 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 Drosophila genetic tools to down-regulate CBS expression and evaluate its behavioral response to light.

Results

We show that CBS-deficient flies do not display the normal stereotypical behavior of attraction towards a luminous source, known as phototaxis. This behavior cannot be attributed to a motor or olfactory deficiency, but it is most likely related to a lower visual acuity. CBS-deficient flies are overall smaller, but smaller eyes do not explain their lack of phototactic response.

Conclusions

The vision phenotype of CBS knock-down flies is consistent with severe myopia in homocystinuria patients. We propose to use Drosophila as a model to investigate ocular manifestations underlying homocystinuria.

KEYWORDS:

• Cystathionine β-synthase
• classical homocystinuria
• Drosophila melanogaster
• phototaxis
• myopia

Acknowledgments

We thank Holly Brown-Borg (University of North Dakota) for sharing an aliquot of the CBS antibody and Porfirio Nava Domínguez (Cinvestav, Mexico) for sharing reagents and equipment for the Western blot experiments. This work was funded with institutional support from the Center for Research and Advanced Studies (Cinvestav), Mexico. Marycruz Flores-Flores and Leonardo Moreno-García were recipients of a Masters of Science scholarship from the Consejo Nacional de Ciencia y Tecnología of Mexico (CONACyT).

Declaration of interest statement

The authors declare no competing interests.

Additional information

Funding

This work was supported by the Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional; Consejo Nacional de Ciencia y Tecnología.