CYP1B1R368H and Glaucoma Development: Functional Evidence from Drosophila

Glaucoma considered as the second foremost cause of bilateral blindness worldwide. Primary open-angle glaucoma (POAG) is the most common form of the disease which is associated with increased intra-ocular pressure and progressive loss of vision owing to retinal ganglion cell demise. Considering the heterogeneity of glaucoma, there are number of characterized genetic mutations contributing to the disease development. MYOC gene is the main causative gene for POAG, but many studies revealed the role of CYP1B1 gene mutations in POAG with diverse incidence in different populations. There is a controversy for the role of CYP1B1R368H mutation in different types of glaucoma. Even though in some studies this mutation categorized as causal mutation, there are other investigations report it as non-pathogenic SNP. Therefore, functional in vivo evaluations can unravel the CYP1B1R368H possible role in POAG development. Unique and highly applicable genetic features of Drosophila melanogaster interested us to use this tiny insect as a model system to study the effects of R368H mutation of CYP1B1 on eye structure and function. The UAS-hCYP1B1WT and UAS-hCYP1B1R368H transgenic flies are being developed to facilitate over-expression of the target gene in compound eye structure of the Drosophila by making use of GMR-Gal4 driver. This fly model will enable us to investigate molecular mechanisms underlies CYP1B1R368H mutation pathogenicity in glaucoma.