Professor Ohnuma summarises the findings of this important project
Although there are a range of successful treatments available for retinoblastoma, unfortunately many of these can cause some degree of vision loss for the child. In order to be able to develop new treatments, that also preserve healthy vision, we need to understand more about how retinoblastoma forms.
Cancer is known to be formed through the accumulation of mutations of important genes. It is already known that mutation of the RB1 gene is crucial for the development of retinoblastoma. To gain a more detailed picture of the gene mutations involved in Rb, we analysed whole sequences of retinoblastoma patient DNA. To our surprise we found that only two genes were mutated. This is different from other types of cancer. It is known that RB1 mutation is not sufficient on its own to initiate retinoblastoma in children. Our results indicate that additional mechanisms other than gene mutation are required for retinoblastoma to develop.
When we examined these mechanisms in detail, we found that almost all cancer-related mechanisms are activated in retinoblastoma. In addition, we found that whilst a protein called PRELP is highly expressed in normal retinal tissues, it is not expressed in retinoblastoma. PRELP plays an important in cell to cell adhesion (where cells interact and attach to neighbouring cells). The fact that it is strongly decreased in retinoblastoma indicates that this decrease enables the Rb cells to grow freely in the patient’s eye. Our study proposes that reversing this, by activating cell to cell adhesion, may have potential as a treatment of retinoblastoma.
Preliminary data from cell cultures indicate that administration of PRELP to the established laboratory retinoblastoma cell lines inhibits cancer progression. We have now been awarded CHECT funding to explore this further, this time applying PRELP protein to human retinoblastoma tissues and examining the effect on retinoblastoma development.
If successful, we hope these findings will lead to the development of new treatments for retinoblastoma that would preserve more of the child’s healthy vision.
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