title: Histopathology and vascular endothelial growth factor in untreated and diode laser-treated retinopathy of prematurity.
abstract: OBJECTIVE
  We had the unique opportunity to compare the eyes of a premature infant with stage 3 retinopathy of prematurity (ROP) in both eyes after the condition was treated by diode laser photocoagulation in one eye only. After the infant's death, we investigated the extent of structural damage incurred with the diode laser and examined the effect of treatment on vascular endothelial growth factor (VEGF) expression.
  
  
  METHODS
  The eyes were fixed and embedded in paraffin. Adjacent 6 microns sections were either stained for histopathologic analysis or used for in situ hybridization. VEGF messenger RNA (mRNA) was detected by using radiolabeled antisense riboprobes.
  
  
  RESULTS
  In the treated eye, histopathologic results demonstrated the clinically evident dose-response effect, with sparing of inner retinal elements with mild laser burns and full-thickness retinal cell disruption with severe burns. Scleral and ciliary nerve effects were absent. VEGF mRNA was localized primarily in the ganglion cell layer but was also found in the inner nuclear layer. In the untreated eye, an increase in VEGF mRNA was detected at the peripheral edge of the vascularized retina anterior to the ridge. In the laser-treated eye, VEGF mRNA expression was dramatically upregulated in the ganglion cell layer in areas adjacent to laser burns.
  
  
  CONCLUSIONS
  VEGF mRNA was found to be elevated in the peripheral, avascular retina of the untreated eye, consistent with the hypothesis that retinal hypoxia stimulates VEGF expression. In the treated eye with recurrent ROP, VEGF mRNA was not detected in the photocoagulated areas of retina but was increased between laser scars. This finding confirms the results of prior animal studies and validates the use of these models.
authors.affiliation: Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Young
authors.forename: D C
authors.initials: DC
authors.lastname: Anthony
authors.forename: E
authors.initials: E
authors.lastname: Pierce
authors.forename: E
authors.initials: E
authors.lastname: Foley
authors.forename: L E
authors.initials: LE
authors.lastname: Smith
mesh_terms: D000328:Adult; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007231:Infant, Newborn; D017075:Laser Coagulation; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D012008:Recurrence; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D014310:Triplets; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors