Timed topical dexamethasone eye drops improve mitochondrial function to prevent severe retinopathy of prematurity
Pathological neovascularization in retinopathy of prematurity (ROP) can cause visual impairment in preterm infants. Current ROP treatments which are not preventative and only address late neovascular ROP, are costly and can lead to severe complications. We showed that topical 0.1% dexamethasone eye drops administered prior to peak neovessel formation prevented neovascularization in five extremely preterm infants at high risk for ROP and suppressed neovascularization by 30% in mouse oxygen-induced retinopathy (OIR) modeling ROP. In contrast, in OIR, topical dexamethasone treatment before any neovessel formation had limited efficacy in preventing later neovascularization, while treatment after peak neovessel formation had a non-statistically significant trend to exacerbating disease. Optimally timed topical dexamethasone suppression of neovascularization in OIR was associated with increased retinal mitochondrial gene expression and decreased inflammatory marker expression, predominantly found in immune cells. Blocking mitochondrial ATP synthetase reversed the inhibitory effect of dexamethasone on neovascularization in OIR. This study provides new insights into topical steroid effects in retinal neovascularization and into mitochondrial function in phase II ROP, and suggests a simple clinical approach to prevent severe ROP.
Authors
- Gaël Cagnone (ORCID: https://orcid.org/0000-0001-9664-3518)
- Myriam Boeck (ORCID: https://orcid.org/0000-0001-8343-4426)
- Zhongjie Fu (ORCID: https://orcid.org/0000-0002-8182-2983)
- Sasha A. Singh (ORCID: https://orcid.org/0000-0003-0929-3164)
- Ann Hellström (ORCID: https://orcid.org/0000-0002-9259-1244)
- Pia Lundgren (ORCID: https://orcid.org/0000-0002-7731-1988)
- Katherine Neilsen
- Yohei Tomita (ORCID: https://orcid.org/0000-0003-1013-5737)
- Hitomi Yagi (ORCID: https://orcid.org/0000-0002-5199-1970)
- Masanori Aikawa (ORCID: https://orcid.org/0000-0002-9275-2079)
- Kazuno Negishi (ORCID: https://orcid.org/0000-0002-2892-9810)
- Jean‐Sébastien Joyal (ORCID: https://orcid.org/0000-0003-3877-9614)
- Taku Kasai (ORCID: https://orcid.org/0000-0002-8075-6099)
- Lois E. H. Smith (ORCID: https://orcid.org/0000-0001-7644-6410)
- Mariya Petrishka-Lozenska
- Jeff Lee
- Chaomei Wang
Institutions
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Keio University (JP)
- Sahlgrenska University Hospital (SE)
- University Medical Center Freiburg (DE)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Université de Montréal (CA)
- University of Gothenburg (SE)
Publication Details
- Journal
- Angiogenesis
- Published
- 2024-09-17
- DOI
- https://doi.org/10.1007/s10456-024-09948-2
- Citations
- 6
- Primary Topic
- Retinopathy of Prematurity Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.43
Funders
- Boston Children's Hospital
- Massachusetts Lions Eye Research Fund
- Ögonfonden
- Kowa Company
- Svenska Forskningsrådet Formas
- Vetenskapsrådet
- National Institutes of Health
- Intellectual and Developmental Disabilities Research Center