June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
A two-step model of PVL and ROP
Author Affiliations & Notes
  • Weilin Song
    Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, United States
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • George Hoppe
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Demiana Hanna
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Jonathan E Sears
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Weilin Song, None; George Hoppe, None; Demiana Hanna, None; Jonathan Sears, None
  • Footnotes
    Support  An Unrestricted Grant Award from Research to Prevent Blindness RPB1508DM, Foundation Fighting Blindness Center Grant CCMM08120584CCF, NIH NEI P30 Core Center Grant IP30EY025585, The Hartwell Foundation Individual Biomedical Research Award, NIH NEI R01EY024972, RPB Physician Scientist Award # RPB1081JS, RPB Medical Student Eye Research Fellowship.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3001. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Weilin Song, George Hoppe, Demiana Hanna, Jonathan E Sears; A two-step model of PVL and ROP. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3001.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose : Although both the retina and the brain are central nervous system tissues, pathology of each created by preterm birth is ascribed different etiologies. Retinopathy of prematurity (ROP) is created by a two-step mechanism of oxygen induced retinovascular growth attenuation and vasoobliteration (phase 1) followed by ischemic hypoxia and pathological angiogenesis (phase 2). However, the current hypothesis of the etiology of periventricular leukomalacia (PVL) relies on hypoxic ischemia alone that drives inflammation and hypomyelination. We have noted a similar metabolic response of brain cortical astrocytes and retinal Müller cells during hyperoxia, which stimulated the idea that the pathogenesis of PVL may resemble the two-step origin of ROP. In this study, we have developed a murine PVL model to correlate retinal and brain pathology using phase 1 hyperoxia and phase 2 relative hypoxia.

Methods : C57BL/6J pups and their nursing dam were placed into 80% oxygen from P4-P8, control pups from the same litter were placed with a second nursing dam. Dams were switched every 24 hours. Brains and retinas were dissected at P8 and P11. Brain tissue was processed for immunofluorescence staining (MBP, lectin, GFAP, Caspase 3) and western blots (CD31, HIF-1a). Retinal vasculature was revealed by lectin staining. Immunofluorescent images of brain and retina were analyzed with ImageJ and AngioTool. Statistical analysis was performed by comparing means using Student’s t-test.

Results : Mice in the hyperoxia group demonstrated hypomyelination and increased apoptosis in periventricular zones at P8 and P11. Astrocytes demonstrated decreased GFAP expression at P8 compared to normoxic controls but increased expression at P11, consistent with PVL. Hyperoxic mice also had decreased cerebral capillary density on the roof of the lateral ventricles with decreased CD31 and HIF-1a expression. Retinal vasculature contemporaneously revealed vaso-obliteration at P8.

Conclusions : A two-step model of PVL using hyperoxia followed by relative hypoxia results in hypomyelination, decreased cerebral capillary density, and downregulation of HIF-1a. These findings support the hypothesis that hyperoxia results in dysregulation of periventricular vasculature development and hypomyelination and provides an experimental correlate of PVL.

This is a 2021 ARVO Annual Meeting abstract.


This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.