The Glaucoma Genetics Lab is working with the Tucker Stem Cell Lab to study glaucoma. Together we have developed a research program to study our glaucoma patients’ eye disease using cells cultured from their skin.
We have obtained small skin biopsies from our patients that have glaucoma due to a TBK1 gene mutation and we are growing skin cells (fibroblasts or keratinocyte progenitor skin cells) from these biopsies.
- We have reprogrammed the skin cells to become adult pluripotent stem cells (iPSCs) by forcing the cells to express 4 transcription factor genes (the Yamanaka factors).
- We have differentiated the iPSCs into neurons that express the markers of retinal ganglion cells (BRN3B, ST100, and BRN3B).
These cells are a powerful tool to study glaucoma caused by TBK1 gene mutations. We are studying the effects of a TBK1 gene duplication on basic biology in these retinal ganglion cells that we have produced from our patients.
We are using these cells to investigate the effects of a TBK1 gene duplication on autophagy, a process by which cells recycle their basic components.
We are also using these cells to test the safety and effectiveness of drugs that inhibit TBK1 activity.
These experiments are the first steps towards developing new sight-saving therapies.