Members of the laboratory of Qi Cui, MD, PhD. From left to right: Michelle Guo (Penn MD candidate), Emily Lawrence (Penn MD Candidate), Qi Cui, Jie Wu, and Turner Schwartz (Penn MD Candidate).
By Alexandra Brodin
Scheie Vision Annual Report 2021
In February 2021, Qi Cui, MD, PhD received the $50K Glaucoma Research Foundation (GRF) Shaffer Grant for Innovative Glaucoma Research. Her project, titled “Evaluating the Glucagon-like Peptide 1 Receptor (GLP-1R) as a Therapeutic Target in Glaucoma,” will help to determine the translational potential of a well-known diabetes drug to treat glaucoma. Dr. Cui is an Assistant Professor of Ophthalmology specializing in glaucoma at the Scheie Eye Institute. Her project is one of nine selected by the GRF to receive the Shaffer Grant this year.
Glaucoma, a complex group of eye diseases, is the leading cause of irreversible blindness worldwide. It is characterized by damage to the optic nerve resulting from the death of retinal ganglion cells (RGCs), often due to high intraocular pressure (IOP). Many of the underlying mechanisms of glaucoma, including genetic susceptibility, are not fully understood. In addition, the standard treatment of lowering IOP is not effective in a subset of patients, whose glaucoma may continue to progress even after reaching normal IOP levels.
Dr. Cui and her team previously found that a class of medications known as GLP-1 receptor agonists had a neuroprotective effect in mouse models of glaucoma, effectively reducing RGC death. They hypothesized that NLY01, a novel GLP-1 receptor agonist, which is a drug class used to treat type 2 diabetes that was recently approved to help with weight loss, may be protective against RGC death.
For this project, Dr. Cui’s team plans to test the protectiveness of NLY01 in a different mouse model of glaucoma to determine if NLY01 offers longitudinal protection. In collaboration with Brian VanderBeek, MD, MPH, MSCE, a retina specialist at Scheie, she will also retrospectively evaluate existing data on patients who have taken this drug for type 2 diabetes to see if they have experienced neuroprotective effects.
Another aim of Dr. Cui’s grant is to test whether these drugs exert their effect by dampening the activity of myeloid cells in the brain and the retina. “We think the microglia and macrophages within the retina work to convert astrocytes, an important class of support cells within the central nervous system, into a form that can be toxic to ganglion cells,” explained Dr. Cui.
Of note, glaucoma shares similarities with other types of neurodegenerative conditions, such as Alzheimer’s and Parkinson’s disease. Research shows that the type of neuroinflammation observed in mouse models of glaucoma also occurs in mouse models and human eyes of individuals with these other conditions. NLYL01 is currently in clinical trials to treat Alzheimer’s and Parkinson’s, as it appears to reduce neuroinflammation.
“One reason that we are excited about this project is that it has considerable translational potential,” said Dr. Cui. “This is a class of medication that is already in use clinically, and its safety data has been collected for over 15 years.”
Considering the complex nature of glaucoma, as well as the potential for severe, irreversible vision loss, advancing novel therapies for this disease is paramount. Dr. Cui’s grant shows great promise for translating existing medications to help prevent RGC death and blindness due to glaucoma.
References
Sterling, JK, Adetunji, MO, Guttha, S, Bargoud AR, Uyhazi, KE, Ross, AG, Dunaief, JL, Cui, CN. GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension. Cell Rep. 2020;33:108271.