Improved blood vessels in retinopathy with targeted approach

2021-05-05

Treatment of the eye disease, retinopathy, aims to reduce the formation of blood vessels in the retina of the eye. To reduce unwanted side effects of such treatments, researchers in Lena Claesson-Welsh’s research group have tested to inhibit the enzyme eNOS and found a reduced formation of dysfunctional vessels in mice with retinopathy while the healthy vasculature in the retina was preserved. The study highlights the importance of targeted approaches in medicine.

In retinopathy, increased blood vessel growth leads to vision loss and if left untreated, eventually to blindness. The disease can affect premature babies, diabetic patients and in some cases it is hereditary.

The blood vessel growth is caused by an increased production of the protein, vascular endothelial growth factor (VEGF). VEGF stimulates growth and leakiness of blood vessels and the leakiness causes edema, harming the sensitive eye tissue.

Retinopathies are increasingly treated by different drugs that suppress the action of VEGF (called anti-VEGF). However, despite the success of anti-VEGF drugs in a clinical setting, they are associated with side effects such toxic effects on both endothelial cells in blood vessels and on neuronal cells in the retina. Since anti-VEGF treatment affects several different types of cells, the use of anti-VEGF can, in this regard, be likened to using a shotgun to kill a mosquito. It is therefore important to identify treatments that specifically target VEGF’s effect on blood vessel cells and in the new study the researchers have focused on the enzyme eNOS.

“eNOS stands for endothelial nitric oxide synthase. It is a VEGF regulated enzyme which is expressed only in endothelial cells in blood vessels. In the study we inhibited eNOS genetically or with a drug and observed a significant reduction in the formation of dysfunctional vessels in mice with retinopathy,” says Lena Claesson-Welsh, who led the study.

The remaining pathological vessel leaked less, preserving the healthy vasculature in the retina. To more closely mimic a clinical situation, the researchers also tested to administer the eNOS inhibiting drug to mice with established pathological vessels and found that the vascular leakage decreased.

Image showing the retinal vasculature (blue) and
fluorescent beads that have leaked (red) in a mouse
retina.

“This study highlights the importance of targeted approaches that only have an effect where they are needed. This applies not only to the treatment of retinopathy, but in medicine as a whole,” says Dominic Love, a researcher in the Claesson-Welsh lab.

The study has been published in the scientific journal eLife and was done in collaboration with researchers in Germany and USA.

More information:
Article in eLife
Lena Claesson-Welsh’s research