© iStockphoto.com/Jack_Zhang
The optic disc is the part of the eye in which retinal neurons extend their branches to leave the retina and enter the brain. Individuals with certain kinds of visual dysfunction, such as nearsightedness and glaucoma, tend to have larger optic discs than individuals with normal vision. Chiea Chuen Khor at the A*STAR Genome Institute of Singapore and co-workers have now identified genetic variations in three genes that can affect the size of the optic disc in Singaporean and Caucasian individuals.
Recent studies have identified genes that affect optic disc size in Caucasian populations. However, it was unclear if those same genes would also play a role in Asians, as there are substantial differences in eye shape and anatomy between Asian and Caucasian populations. In addition, some diseases of vision, including nearsightedness and glaucoma, tend to be more common in Asian populations than in Caucasians.
The researchers performed a genome-wide association study (GWAS) of almost 4,500 Singaporean individuals; half were of Malay ancestry, and the other half were of Indian ancestry. They found three genes that were correlated with increased optic disc size in this population. Two of these genes, CDC7/TGFBR3 and ATOH7, had already been identified in a previous GWAS of Caucasian individuals. However, the researchers also found a new association of disease with variation in the Caspase recruitment domain-containing protein 10 (CARD10) gene in the Singaporean population. The variation on CARD10 also seemed to be linked to optic disc area in Caucasian individuals from the Netherlands, albeit with a slightly weaker effect.
“The identification of these genes governing ocular traits could be the first step toward an improved understanding of the glaucoma disease mechanism, the most common cause of blindness worldwide,” explains Khor.
The CARD10 protein regulates the death of cells by controlling the activation of proteins called caspases. CARD10 can be found at the cell membrane, and its job is to add phosphate groups to other proteins in order to initiate the creation of protein complexes, which affect cell signaling. For example, CARD10 can activate the transcription factor NFκB, triggering a signaling pathway that has been shown to play a key role in nervous system development and in various neurodegenerative diseases. Future work will be necessary in order to uncover how the observed variation in the CARD10 gene could affect cell death in the retina, and possibly predispose individuals to the development of visual dysfunction.
The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore.
