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.
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
-
Rare genetic variants are not the main cause of common diseases
2022-05-13
Although some rare variants can significantly increase the risk of disease for a few individuals, the majority of the genetic contribution to common diseases is due to a combination of many common genetic variants with small effects. This is shown by researchers at IGP and other departments at Uppsala University in a new comprehensive study published in the journal Nature Communications.
-
Subgroups of brain tumours associated with cell origin and disease prognosis
2022-04-25
Researchers at IGP have detected different subgroups of the brain tumour form glioblastoma, where the cancer cells’ properties depend on which cell type they originate from. The used analysis method could also separate glioblastoma patients with significant differences in survival. The findings open up for identifying specific therapeutic targets for the new subgroups of glioblastoma.
-
Armed CAR-T cells to better fight cancer
2022-04-04
Immunotherapy is increasingly becoming a successful way to treat cancer. Researchers at IGP have now developed armed CAR-T cells that reinforce the immune defence against cancer and that could increase the possibilities to successfully treat solid tumours. The study has been published in the journal Nature BioMedical Engineering.
-
Inflammation and net-like protein structures in cerebral cavernous malformations
2022-03-28
In the condition known as cavernoma, lesions arise in a cluster of blood vessels in the brain, spinal cord or retina. Researchers at IGP now show in a new study that white blood cells and protein structures associated with the immune response infiltrate the vessel lesions. The findings support that inflammation has a role in the development of cavernoma and indicate a potential biomarker for the disease.
-
Protein landscape on cancer cells mapped with new technology
2022-03-03
In recent years, great advances have been made in the development of new, successful immunotherapies to treat cancer. Two types of targeted immunotherapies that have revolutionised areas of cancer care are CAR T-cell therapy and antibody treatments. However, there are still significant challenges in the identification of cancer cell surface proteins that function as targets for immunotherapies. Mattias Belting, professor at Lund University and senior consultant at Skåne University Hospital, and guest professor at IGP, is well on the way and his group’s findings are now published in the journal PNAS.
-
CRISPR-Cas9 can generate unexpected, heritable mutations
2022-02-03
CRISPR-Cas9, the “genetic scissors”, creates new potential for curing diseases; but treatments must be reliable. In a new study, researchers have discovered that the method can give rise to unforeseen changes in DNA that can be inherited by the next generation. These scientists therefore urge caution and meticulous validation before using CRISPR-Cas9 for medical purposes.
-
New technology to study DNA in archived tissue samples
2022-01-19
Researchers at IGP have developed a technology that allows studies of DNA profiles in archived tissue samples. The technology permits investigators to better understand regulation of gene activity in cancer and precision medicine.
-
New genes associated with relapse of acute myeloid leukemia
2022-01-13
In the blood cancer type acute myeloid leukemia, it is common that patients relapse some time after treatment. Researchers from IGP have in a new study identified genes that seem to be associated with the risk of relapse. The findings may form the basis for new treatment strategies and contribute to better survival for patients with acute myeloid leukemia.