Strategies to Prevent Vascular Damage in Phase I Retinopathy of prematurity
Research details
- Type of funding: PhD Studentship
- Grant Holder: Dr Denise McDonald
- Institute: Queen's University Belfast (QUB)
- Region: Northern Ireland
- Start date: October 2018
- End Date: October 2022
- Priority: Causes
- Eye Category: Childhood-onset
Retinopathy of prematurity (ROP) is a sight-threatening complication of premature birth. This disease occurs in two phases:
(1) Early: Premature infants are exposed to high oxygen, which damages the endothelial cells (EC) essential for blood vessel formation. This results in the light sensitive cells in the retina becoming ischaemic/hypoxic when oxygen treatment is withdrawn.
(2) Late: The surviving blood vessels proliferate in an attempt to rescue the hypoxic retina in a disordered manner that, if untreated, causes permanent vision loss.
Current treatments focus on the late phase, but with limited success and significant side effects, this demonstrates a need for new therapies. Studies show that the late stage of disease is dependent on the extent of vessel damage in the early phase and is far more severe in infants with more vessel loss in the early phase. Together, this indicates that an improvement in the initial early phase would lessen the severity of the late phase.
Researchers have discovered that a protein called Fbxw7 is greatly enhanced in EC subject to hyperoxia. Fbxw7 acts as a crucial hub that controls how a cell proliferates or matures. They aim to find a therapy that will protect the vessels in the early phase.
Isolated vascular cells and in vivo models mimicking ROP, will be used to investigate how Fbxw7 is regulated by hyperoxia and to investigate the ways of modulating its function in order to protect the blood vessels of the eye from the harmful consequences of hyperoxia.
Any reduction in the extent of the early phase will reduce the severity of ROP and would have a significant impact on the quality of life for all infants affected.
Additionally, high oxygen is detrimental to the maturing lungs of premature infants, causing a disease called bronchopulmonary dysplasia which is associated with the under development of blood vessels in the lung. Thus, the outcomes will have an important impact on strategies aimed at reducing oxygen induced arrested alveolar/ lung growth in neonates.
(1) Early: Premature infants are exposed to high oxygen, which damages the endothelial cells (EC) essential for blood vessel formation. This results in the light sensitive cells in the retina becoming ischaemic/hypoxic when oxygen treatment is withdrawn.
(2) Late: The surviving blood vessels proliferate in an attempt to rescue the hypoxic retina in a disordered manner that, if untreated, causes permanent vision loss.
Current treatments focus on the late phase, but with limited success and significant side effects, this demonstrates a need for new therapies. Studies show that the late stage of disease is dependent on the extent of vessel damage in the early phase and is far more severe in infants with more vessel loss in the early phase. Together, this indicates that an improvement in the initial early phase would lessen the severity of the late phase.
Researchers have discovered that a protein called Fbxw7 is greatly enhanced in EC subject to hyperoxia. Fbxw7 acts as a crucial hub that controls how a cell proliferates or matures. They aim to find a therapy that will protect the vessels in the early phase.
Isolated vascular cells and in vivo models mimicking ROP, will be used to investigate how Fbxw7 is regulated by hyperoxia and to investigate the ways of modulating its function in order to protect the blood vessels of the eye from the harmful consequences of hyperoxia.
Any reduction in the extent of the early phase will reduce the severity of ROP and would have a significant impact on the quality of life for all infants affected.
Additionally, high oxygen is detrimental to the maturing lungs of premature infants, causing a disease called bronchopulmonary dysplasia which is associated with the under development of blood vessels in the lung. Thus, the outcomes will have an important impact on strategies aimed at reducing oxygen induced arrested alveolar/ lung growth in neonates.