– Sidrat Tasawoor Kanth
Microspherophakia (MSP) is a rare genetic disorder characterised by a smaller-than-normal spherical lens in the human eye, which can lead to glaucoma and sometimes blindness. Researchers led by Upendra Nongthomba and Arun Kumar, Professors at the Department of Molecular Reproduction, Development and Genetics at IISc, have now identified a new gene responsible for this disorder.
In collaboration with the Prabha Eye Clinic and Research Centre, Bangalore, the IISc team identified two families whose members exhibited this abnormality. Advanced genetic analysis indicated that mutations in a particular gene (WRAP73/WDR8) were linked to the disorder. To verify this, they replicated the disorder conditions in a commonly used model organism, the zebrafish, by removing the identified gene from its genome. Subsequently, a reduction in eye size, as seen in MSP, was recapitulated in these zebrafish. The authors found that knocking out thegene prevents the stability of a protein required during cell division and arrests retinal cell development, resulting in a smaller eye size. The team then inserted the corresponding human gene fragment into the affected fish. This reversed the symptoms of the disorder, hence confirming the role of the WDR8 gene in causing Microspherophakia.
Though the exact mechanisms by which the WDR8 gene regulates the early development of the eye are yet to be found, these results may pave the way for early diagnosis and therapeutic remedies for Microspherophakia.
M. Madhangi, Debanjan Dutta, Sautan Show, Vishwanath K Bhat, Mohammad I. Rather, Ankana Tiwari, Nivedita Singh, Maheswara R. Duvvari, Gowri J. Murthy, Arun Kumar, Upendra Nongthomba, Exome sequencing and functional studies in zebrafish identify WDR8 as the causative gene for isolated Microspherophakia in Indian families. Human Molecular Genetics, 2021.