When it comes to vision diseases, such as glaucoma or macular degeneration, there isn’t one exact cause that leads to their development. Usually, it is a combination of factors, such as genetics, lifestyle and in some cases, medications with steroids can lead to glaucoma. Of course, it would be ideal to learn more about the causes of these diseases in order to develop treatments that improve outcomes. Research projects at Cornell and Washington University in St. Louis are looking to learn more about the causes of these disease and ways to prevent them.
Eye on a Chip
When eye drainage is compromised, glaucoma develops. Some anti-inflammatory eye medications that contain steroids can lead to glaucoma, and scientists want to find out why. Scientists in the lab of Esak (Isaac) Lee, assistant professor of biomedical engineering at Cornell Engineering, created a 3D eye on a chip platform that copies the flow of eye fluids.
The usual way of studying glaucoma, either in animal models or in 2D cells cultures, don’t show the complexity of the human eye. Lee’s lab made a 3D in-vitro model that can copy the eye’s layered structures while isolating biological and physical factors in a reproducible and controlled manner.
When the eye’s lymphatic vessels don’t work properly, intraocular pressure can increase, and damaging the neurons in the retina needed to transmit light signals to the brain. Researchers built a 3D in-vitro device, called microphysiological system (MPS), with a double layer of Trabecular Meshwork (TM) and Schlemm’s Canal (SC) cells. It also has a curvature that copies the conduit structure of the lymphatic vessels in the eye. They gave this device the anti-inflammatory steroid dexamethasone and it damaged the drainage system.
Observing the damage caused made by dexamethasone allowed scientists to determine why it occurred. Namely, a key receptor in the TM cell, known as ALK5, responded to the steroid by downregulating the protein vascular endothelial growth factor C (VEGFC). When VEGFC works properly, it loosens the endothelial junctions in SC cells, allowing fluid to pass through the endothelial wall. The steroid tightened the junctions in Schlemm’s canal, increasing resistance to outflow, which leads to glaucoma.
This discovery provides two possible options to treating glaucoma. One option is to block the ALK5 function. Another is to provide additional VEGFC to the eye along with steroid treatment.
Cholesterol Metabolism & Macular Degeneration
Too much cholesterol isn’t good for you. We all know that fact. Thanks to work done at the Washington University School of Medicine in St. Louis, researchers found that problems with cholesterol metabolism can lead to age-related macular degeneration.
This study suggests that increasing the amount of a molecule called apolipoprotein M (ApoM) in the blood repairs the problem of cholesterol processing that can cause cellular damage in organs, such as the eyes.
When someone has macular degeneration, eye doctors can see cholesterol deposits under the retina during an eye exam. While vision may still be normal during the early stages, the deposits increase inflammation and other processes that slowly lead to the loss of central vision. Recent research has shown that ApoM can utilized as a protective molecule in maintaining healthy cholesterol metabolism, since it has anti-inflammatory effects. Scientists wanted to determine whether reduced ApoM levels, (ApoM decreases as we age) could be involved in dysfunctional cholesterol metabolism that leads to macular degeneration and other diseases of aging.
Researchers found that patients with macular degeneration had reduced levels of ApoM, compared to healthy control subjects. The study suggests that when ApoM is low, retinal cells can’t correctly metabolize cholesterol deposits and have difficulty eliminating accumulating lipids. When the lipids build up, it leads to inflammation and cellular damage.
Scientists in this study increased ApoM level in mouse models of macular degeneration using genetic modification or plasma transfer from other mice. The mice showed improvement in retinal health, improved function of light sensing cells and reduced accumulation of cholesterol of deposits. Scientists also found that ApoM triggers a signaling pathway that down cholesterol into lysosomes, which play a role in disposing of cellular waste.
“Current therapies that reduce the chance of further vision loss are limited to only the most advanced stages of macular degeneration and do not reverse the disease,” said senior author Rajendra S. Apte, MD, PhD, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences at Washington University School of Medicine. “Our findings suggest that developing treatments that increase ApoM levels could treat or even prevent the disease and therefore preserve people’s vision as they age.”
These research projects show that learning about the causes of vision diseases, such as glaucoma and macular degeneration can lead to treatments that do more than simply maintain remaining vision. Work at Cornell could lead to additional treatment options for glaucoma. Work at Washington University School of Medicine shows that increasing ApoM might help preserve vision as a person ages. Thanks to these studies, people diagnosed with glaucoma or macular degeneration may no longer have to accept “learn to live with it” as their only option.
Sources:
https://news.cornell.edu/stories/2025/08/eye-chip-reveals-trigger-steroid-induced-glaucoma
https://medicine.washu.edu/news/strategy-to-prevent-age-related-macular-degeneration-identified/