Growing Human Retinal Organoids to Study Retinal Ganglion Cell Birth and Death in Glaucoma

Summary

During glaucoma, the neurons that connect the eye to the brain die, leading to vision loss. We have learned a great deal about these cells from studies in other animals like mice and fish, yet studies directly in developing human tissue have been limited. Here, we propose to grow human retinas in a dish from stem cells to (1) determine what genes are on or off in these critical neurons, (2) develop treatments to increase the number of these neurons, and (3) study how these neurons die and develop ways to prevent their death. Our work will be the first to study these mechanisms in developing human tissue, providing insights critical for understanding glaucoma progression and therapeutic applications.

Project Details

My research program is dedicated to understanding how the cell types of the human retina are generated and incorporating this knowledge into the development of retinal organoid technology for visual restoration therapies.

My lab grows human stem cells into retinas in a dish. These mini-retinas are called "retinal organoids". Human retinal organoids hold huge promise for therapeutic treatments for sufferers of glaucoma. In particular, we are trying to understand the biology of retinal ganglion cells (RGCs), the cells that die during glaucoma.

The first step to understanding the utility of retinal organoids is to determine how they recapitulate normal retinal development. To achieve this goal, we are characterizing the types of RGCs generated in organoids by analyzing which genes are on or off across individual cells. The next goal is to promote the generation of RGCs. During our previous studies of human photoreceptor cells, we identified conditions that promote specialized regions of the retina that display high numbers of RGCs. We will test these conditions in organoids and look for increases in the generation of RGCs. Finally, the death of RGCs in glaucoma is a true challenge to overcome. Interestingly, RGCs die in organoids and we hypothesize that they die in a similar manner during glaucoma. We will directly compare death of RGCs in glaucoma and in organoids and tests ways to prevent death in organoids.

My lab advanced human retinal organoids as a model to study photoreceptor specification during human development. My lab is among the leaders in the world using this innovative technology to study human biology. We are in a unique position to study RGC biology with potential for glaucoma prevention and vision restoration therapy.

Our studies will directly impact our understanding of RGC biology and glaucoma. Our work will be the first to study the mechanisms of RGC specification and death in developing human tissue, providing insights critical for understanding glaucoma progression and therapeutic applications.