Abstract
Background
Retinopathy of prematurity (ROP) remains the leading cause for blindness in children. Limited hyperoxia induced proliferative retinopathy (L-HIPR) was recently introduced as a potential animal model for ROP and persistent fetal vasculature; however, the detailed pathological changes remain unclear.
Methods
To model L-HIPR, we placed C57BL/6J mice in 65% oxygen from birth to post-natal day 7 (P7). We examined eyes at intervals between P12 and P30. Retinal morphometry, thickness, and preretinal fibrosis were quantified at different time points on histological sections stained with hematoxylin and eosin (H&E) and Masson Trichrome, respectively. Vascular development, angiogenesis, inflammation, and pericyte coverage were analyzed using immunohistochemistry staining in retinal flat mounts and cross sections.
Results
In L-HIPR, the hyaloidal vessels persisted until the latest time point in this study, P30 and began to invaginate the peripheral then central retina starting at P12. Central retinal distortion was noted beginning at P17, while the peripheral retina demonstrated a trend of thinning from P12 to P30. We found that L-HIPR was associated with delayed and abnormal retinal vascular development with subsequent retinal inflammation, pericyte loss and preretinal fibrosis.
Conclusion
Our study presents a detailed analysis of the L-HIPR animal model demonstrating vitreoretinal pathologic changes, preretinal fibrosis and persistent hyaloidal vessels into adulthood. Based on our findings, we suggest that the persistence and peculiar stepwise migration of the hyaloidal vessels into the retina may provide a potential rescue mechanism for inner retinal development that deserves further study.
Funder
National Institutes of Health
illinois society for the prevention of blindness
Publisher
Public Library of Science (PLoS)
Reference18 articles.
1. Animal models of ocular angiogenesis: from development to pathologies;CH Liu;FASEB J,2017
2. Oxygen-induced retinopathy in the mouse;LE Smith;Invest Ophthalmol Vis Sci,1994
3. The mouse retina as an angiogenesis model;A Stahl;Invest Ophthalmol Vis Sci,2010
4. Mechanisms and management of retinopathy of prematurity;ME Hartnett;N Engl J Med,2012
5. Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years;JE Brumbaugh;Pediatric Research,2021
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献