Vision Research

WITH GRATITUDE

I would like to express my gratitude for your generosity. I am truly grateful for your commitment to our important work in developing new treatments and therapies for blinding eye diseases. My clinical work encompasses caring for patients through visits and procedures such as lasers and injections in our clinics, as well as through retinal surgery in our operating rooms. Through this important effort, I understand the many unmet needs our patients still have and what we can possibly do to address them.

Once cells are lost in the retina, through macular degeneration (AMD) and other diseases like cancer in the eye (retinoblastoma), vision loss occurs. We cannot bring those cells back, and thus we cannot restore vision. This is where our research comes in: we want to better understand the biology that makes stem cells turn into the retina, ultimately allowing us to make stem cell-derived retinal transplants a safer and more effective option for retinal diseases like AMD. I’ve included in this report our latest findings and advancements in this field that are made possible through your thoughtful gifts.

With best regards,

Rajesh C. Rao, M.D.

Leonard G. Miller Professor of Ophthalmology & Visual Sciences

Assistant Professor, Ophthalmology & Visual Sciences, Pathology

ADVANCEMENTS IN STEM CELL RESEARCH

This year, your generous support was directed toward assessing how a newly discovered signaling pathway, called the WDR5-p53 cell fate determination pathway, controls the process by which stem cells become the early retina and blocks other cell lineages such as mesoderm (heart and blood and reproductive cells). In November 2019, we learned that our first manuscript on this work was accepted in the prestigious journal Cell Reports. This work has also resulted in provisional US and international patents related to production of tissues from stem cells.

We generated a great deal of data for this work, and we will soon be able to submit a grant application to the National Institutes of Health, the largest funder of biomedical research. This grant is concentrated on how our newly discovered WDR5-p53 pathway pushes stem cells to become retina and not other parts of the central nervous system like the brain and spinal cord. This is important because current stem cell-based therapies are hobbled by their expense: when you generate retina cells, you also generate other types of unwanted brain cells. This makes the process inefficient and potentially unsafe for eventual translation to patient care.

TARGETED THERAPIES

On the ophthalmic pathology side, we have been using human retinoblastoma cells recovered from eyes that were removed due to retinoblastoma cancer and using genetic surgery to remove a gene we believe drives the growth of this tumor. Our work has been encouraging. We have shown that removing this gene can reduce the growth of the cancer cells. The only current treatments for retinoblastoma are injection of chemotherapy into the eye or body, or eye removal surgery. These therapies damage normal tissues as well as retinoblastoma tissues and contribute to vision loss and blindness in children even if the cancer has been successfully treated. Thus, our finding that the new gene (called WHSC1) is required for cells to grow is important.

Since anti-WHSC1 drugs are being developed for other cancers such as multiple myeloma, our findings suggest that WHSC1 might also be a target for retinoblastoma, and thus one of the first targeted therapies for this blinding and deadly disease. We will continue to move forward in this area by identifying which specific part of the gene’s protein is a target that could be used to destroy it.

LOOKING AHEAD

Donor funding will enable our team to further develop a mouse ‘reporter’ strain that will allow us to track and analyze the birth of ‘cone’ cells in the retina. As you know, the loss of cone cells ultimately contributes to vision loss in AMD, and they do not normally regenerate. This special mouse strain will allow us to better understand how cones are born and how we might coax their regeneration in the diseased retina. Your support enables us to maintain our momentum and keep these experiments going. Moving forward, we hope to dedicate a scientist fully to working on this project and purchase additional reagents and new human stem cell lines required for the experiments.

THANK YOU FOR YOUR PARTNERSHIP!

We have achieved so much because of your generosity. To stay up to date on the latest advancements in research, please visit our lab website or social media.