Patel Awarded Funding to Study Corneal Eye Disease

By Dirk Hoffman

Her five-year, $1.8 million R01 grant titled “Corneal Endothelium – Extracellular Matrix Interactions” is from the National Eye Institute.

The cornea is a clear dome on the front of the eye that helps to focus light, thus it needs to maintain perfect clarity for excellent vision.

In FECD, the cornea becomes cloudy because of dysfunction of the cells lining the inside of the cornea (the corneal endothelial cells), and patients require corneal transplantation, Patel says.

FECD is the most common reason for corneal transplantation in the Unites States.

“The first signs of FECD are microscopic mounds of material, called ‘guttae,’ generated by the diseased corneal endothelial cells on the extracellular matrix bed upon which they sit,” Patel says.

“Guttae can be detected during a routine eye exam. FECD is defined by the presence of increasing numbers of guttae in both eyes. The guttae also contribute to the death of the corneal endothelial cells,” she adds.

Despite their central importance in diagnosing FECD, little is understood about how these guttae develop and how they contribute to the dysfunction of the corneal endothelial cells, Patel notes.

“We have discovered a method to generate guttae in extracellular matrix from cultures of corneal endothelial cells in the lab,” she says. “This is the first model to develop guttae in a dish, and we are using this model to better understand the cellular processes that contribute to the development of FECD.”

The study’s specific aims are to use the model Patel’s lab has developed to:

• understand how closely the model of guttae mimics FECD disease in humans
  
• evaluate the cellular pathways that are dysfunctional and cause guttae to form
• analyze how the abnormal extracellular matrix contributes to corneal endothelial cell demise

Currently, FECD can only be treated with corneal transplantation. There are no medications available to prevent or treat this disease.

“In fact, there are no good model systems to use to test potential new therapeutics for FECD before human clinical trials,” Patel says.

“The most significant outcome from this work will be that we will have established a biological model in a dish for the study of the guttae, the primary clinically observable finding in FECD,” she adds. “In addition to allowing us to better understand how guttae form, this can serve as a platform for identifying and testing new therapeutics for FECD.”

Co-investigators on the study are:

• Yongho Bae, PhD, associate professor of pathology and anatomical sciences at the Jacobs School of Medicine and Biomedical Sciences
  
• Jun Qu, PhD, professor of pharmaceutical sciences at UB’s School of Pharmacy and Pharmaceutical Sciences and adjunct assistant professor of biochemistry and ophthalmology at the Jacobs School