June 16, 2024

Why Do Episodes of Low Blood Sugar Worsen Eye Disease in People With Diabetes? Johns Hopkins Unravels the Mystery

Diabetic retinopathy is a progressive eye condition that affects people with diabetes. It occurs when high blood sugar level levels trigger damage to the capillary in the retina, the light-sensitive part of the eye. Diabetic retinopathy can lead to vision loss and even blindness if left without treatment.
People with diabetes who go through episodes of low blood sugar, a common issue for those inexperienced in handling their blood sugar level levels, are more susceptible to a worsening of diabetic eye illness. According to scientists at Johns Hopkins Medicine, they have actually found a connection between these low blood sugar level levels and a molecular pathway that is activated in oxygen-starved cells in the eye.
The study, which was released in the journal Cell Reports, involved human and mouse eye cells and entire retinas grown in a laboratory environment with low sugar (low glucose), along with mice with low glucose levels.
” Temporary episodes of low glucose happen when or two times a day in people with insulin-dependent diabetes and often among individuals newly identified with the condition,” says Akrit Sodhi, M.D., Ph.D., the Branna and Irving Sisenwein Professor of Ophthalmology at the Wilmer Eye Institute at Johns Hopkins Medicine. Low glucose levels can likewise occur throughout sleep in individuals with non-insulin-dependent diabetes. “Our outcomes show that these periodic low glucose levels cause an increase in particular retinal cell proteins, resulting in an overgrowth of capillary and getting worse diabetic eye illness,” adds Sodhi.

It occurs when high blood sugar levels cause damage to the blood vessels in the retina, the light-sensitive part of the eye.” Temporary episodes of low glucose take place when or two times a day in people with insulin-dependent diabetes and typically amongst individuals freshly identified with the condition,” says Akrit Sodhi, M.D., Ph.D., the Branna and Irving Sisenwein Professor of Ophthalmology at the Wilmer Eye Institute at Johns Hopkins Medicine. Low glucose levels can also occur during sleep in individuals with non-insulin-dependent diabetes. “Our results reveal that these routine low glucose levels trigger a boost in specific retinal cell proteins, resulting in an overgrowth of blood vessels and worsening diabetic eye disease,” adds Sodhi.

Eye disease among people with diabetes is amongst the most avoidable causes of blindness in the U.S. Diabetic retinopathy, which takes place in as much as a 3rd of individuals with diabetes, is defined by the overgrowth of irregular capillary in the retina.
Sodhi says the present study suggests that individuals with diabetic retinopathy might be especially susceptible to durations of low glucose, and keeping glucose levels stable ought to be a crucial part of glucose control.
For the study, the researchers examined protein levels in human and mouse retinal cells and intact retinas grown in an environment of low glucose in the lab, in addition to in mice that had periodic low blood sugar level.
The researchers found that low glucose levels in human and mouse retinal cells caused a waterfall of molecular changes that can lead to capillary overgrowth. First, the researchers saw that low glucose caused a decline in retinal cells ability to break down glucose for energy.
When the researchers looked particularly at so-called Müller glial cells, which are helpful cells for nerve cells in the retina and rely mostly on glucose for energy production, they discovered that the cells increased the expression of the GLUT1 gene, which makes a protein that transfers glucose into cells.
The researchers found that, in action to low glucose, the cells increased levels of a transcription element, called hypoxia-inducible element (HIF) -1 α. This switched on the cellular equipment– including GLUT1– required to improve their capability to make use of offered glucose, protecting the limited oxygen available for energy production by retinal neurons.
However, in low-oxygen environments, as occurs in the retinas of clients with diabetic eye disease, this regular, physiologic action to low glucose set off a flood of HIF-1α protein into the cells nucleus, the cells nerve center.
This led to a boost in the production of proteins such as VEGF and ANGPTL4, which trigger the growth of abnormal, leaky blood vessels– the essential culprit of vision loss in people with diabetic eye illness.
The scientists prepare to study whether low glucose levels in people with diabetes may affect similar molecular pathways in other organs, such as the kidney and brain.
Sodhi states the HIF-1α pathway may function as a reliable target for establishing brand-new treatments for diabetic eye disease.
Recommendation: “HIF-1α build-up in action to transient hypoglycemia might aggravate diabetic eye illness” by Chuanyu Guo, Monika Deshpande, Yueqi Niu, Isha Kachwala, Miguel Flores-Bellver, Haley Megarity, Taylor Nuse, Savalan Babapoor-Farrokhran, Michael Ramada, Jaron Sanchez, Neelay Inamdar, Thomas V. Johnson, Maria Valeria Canto-Soler, Silvia Montaner and Akrit Sodhi, 10 January 2023, Cell Reports.DOI: 10.1016/ j.celrep.2022.111976.
Sodhi is a co-founder of and holds equity in HIF Therapeutics Inc. This plan has actually been reviewed and approved by The Johns Hopkins University in accordance with its dispute of interest policies.
The research study was funded by the National Institutes of Healths National Eye Institute, Research to Prevent Blindness, the CellSight Development Fundk, the Doni Solich Family Chair in Ocular Stem Cell Research, and the Branna and Irving Sisenwein Professorship in Ophthalmology.