In the U.S., 38.4 million people have diabetes. Sadly, some of them will develop vision issues related to the diseases, such as a corneal infection known as keratitis or, worse, diabetic retinopathy. It is bad enough to have diabetes and all the complications associated with it. Is there a way to reduce the likelihood of developing these conditions? Scientists are looking for ways develop treatment that will improve outcomes for these conditions.
Researchers at the University of Oklahoma Health Sciences and Memorial Sloan Kettering Cancer Center are working on a treatment for diabetic retinopathy that can be used at an earlier stage than current treatments.
Blindness from diabetic retinopathy is caused by damage to the blood vessels in the eye, which leads to bleeding and lipid buildup. It starts as dark spots in the field of vision, and left untreated, it can lead to retinal detachment, and subsequently, blindness. There are two treatments available for this disease but they are invasive and have side effects. One treatment is the use of lasers to burn the vessels and stop the hemorrhaging. Another treatment involves injections into the eye that stops the progression of the disease. While they are effective in preventing blindness from diabetic retinopathy, they can only be used at a late stage and not everyone responds to these treatments.
Researchers in the lab of Julia Busik, PhD, professor and chair of the department of biochemistry and physiology at the University of Oklahoma Health Sciences looked at the lipid pathways in the retina and how they are affected by diabetes. Her team found that ceramide, a damaging type of lipid was present in the eyes of patients with diabetic retinopathy. In addition, they found that these ceramides, after being stimulated by inflammatory cytokines, stick together and send inflammatory signals to the cells in the eye, which leads to cell death and the development of diabetic retinopathy.
Working with the lab of Richard Kolesnick, MD at Memorial Sloan Kettering Cancer Center, Busik’s lab was able to make an antibody against these lipids to prevent both the buildup of ceramide and damage to healthy cells in the retina. This showed promise in animal and cell culture models. The best part of this discovery is that it focuses on the root cause of the disease and it doesn’t just the stop the progression of diabetic retinopathy at a later stage. Another benefit is that it doesn’t need to be injected into the eye.
Sadly, diabetics have other eye conditions to worry about, such as keratitis, or corneal infection. Diabetics are more than 30 percent likely to get this kind of infection, have a higher rate infection and show increased resistance to some treatments. The lab of Fu-Shin Yu, PhD, professor of ophthalmology, visual and anatomical sciences at the Wayne State University School of Medicine recently received a five-year grant from the National Eye Institute of the National Institutes of Health for his work in reversing the effects of diabetes on eyesight.
Yu’s study, “Role of Programmed Cell Death Pathways in Bacterial Keratitis,” examines the processes that leads to a faulty immune response in the eyes of persons with diabetes and to find ways to reverse them. Scientists in Yu’s lab used mouse models of type 1 and 2 diabetes, as well as Pseudomonas aeruginosa as a model pathogen. This infection is caused by bacteria, it usually occurs in healthcare settings and can be resistant to antibotics. In May 2023 the Centers for Disease Control and Prevention (CDC) confirmed 81 cases of this bacteria strain across 18 states, which resulted in four deaths and 14 cases of vision loss. This stresses the need to learn more about the mechanisms that lead to increased vulnerability to and severity of bacterial keratitis in diabetic patients.
The focus of this research was to understand why diabetic patients are more likely to get a keratitis, why does the disease progress faster in diabetics and why are they more resistant to treatments. Using the type 1 and type 2 mouse models, Yu’s lab found evidence that the mice are likely to get the corneal infections. The looked at RNA sequences in the tissue samples to identify the biological processes. By comparing diabetic pathways to normal pathways, they can learn more about potential treatments.
The ongoing research into diabetic retinopathy and keratitis is a beacon of hope for millions living with diabetes. Scientists like Dr. Busik and Dr. Yu are not only advancing our understanding of these complex conditions, but are also paving the way for innovative treatments that target the root causes. By addressing lipid pathways in diabetic retinopathy and immune dysfunction in keratitis, these groundbreaking studies could significantly improve the quality of life for individuals battling diabetes and its complications.
Sources:
https://www.cdc.gov/diabetes/php/data-research/index.html
https://ou.edu/news/articles/2024/june/potential-new-treatment-option-for-diabetic-retinopathy