Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity

Hitomi Yagi1,2, Myriam Boeck1,3, Mariya Petrishka-Lozenska4

  • 1Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, 3 Blackfan Circle, CLS 18, Boston, MA, 02115, USA.

Angiogenesis
|September 17, 2024
PubMed

Insights

Topical dexamethasone eye drops, given early, can prevent severe retinopathy of prematurity (ROP) in preterm infants. This treatment shows promise for preventing ROP neovascularization and associated vision loss.

Area of Science:

  • Ophthalmology
  • Neonatology
  • Molecular Biology

Background:

  • Pathological neovascularization in retinopathy of prematurity (ROP) leads to vision impairment in preterm infants.
  • Current ROP treatments are reactive, costly, and carry risks of severe complications.

Purpose of the Study:

  • To evaluate the preventative efficacy of early topical dexamethasone for retinopathy of prematurity.
  • To investigate the mechanisms underlying dexamethasone's effects on retinal neovascularization.

Main Methods:

  • Administered topical 0.1% dexamethasone eye drops to high-risk preterm infants and in a mouse model of ROP (oxygen-induced retinopathy - OIR).
  • Assessed neovascularization and measured retinal mitochondrial gene and inflammatory marker expression in OIR.
  • Investigated the role of mitochondrial ATP synthetase by blocking its function.

Main Results:

  • Early topical dexamethasone prevented neovascularization in infants and suppressed it by 30% in OIR.
  • Treatment timing was critical; pre-neovascularization treatment was effective, while later treatment showed limited efficacy or exacerbated disease.
  • Dexamethasone increased mitochondrial gene expression and decreased inflammatory markers in OIR, with effects reversed by blocking ATP synthetase.

Conclusions:

  • Optimally timed topical dexamethasone is a potential preventative strategy for ROP.
  • Dexamethasone's efficacy involves modulation of mitochondrial function and inflammatory pathways.
  • This approach offers a simple, preventative clinical option for severe ROP.