Dexamethasone alters TNF-alpha expression in retinopathy.
TNF-alpha has been found in the retina. Hyperoxia and hypoxia regulate TNF-alpha expression. TNF-alpha is an important factor in inflammation and angiogenesis. Dexamethasone inhibits TNF-alpha production. Changes in TNF-alpha expression in the retina may play an important role in the development of oxygen-induced retinopathy. Oxygen-induced retinopathy was produced in C57BL6 mice by exposure to 75% oxygen at Postnatal Day 7 (P7) for 5 days and the mice recovered in room air until Day 17 (P17). Dexamethasone was administered at 0.5 mg/kg/day once daily subcutaneously during the 5 days of oxygen exposure. TNF-alpha expression was evaluated at Day 7 prior to oxygen exposure, at Day 12 (P12) immediately upon removal from oxygen, and at Day 17, the time of maximal vasoproliferation by RT-PCR. TNF-alpha is developmentally regulated in the retinae of C57BL6 mice. From P7 to P12, there is a 3-fold increase in TNF-alpha expression and from P7 to P17 there is a 2.7-fold increase. There was 2.7-fold suppression in expression immediately following oxygen exposure at P12. The expression was dramatically increased at P17, the time of maximal vasoproliferation. Dexamethasone inhibited the expression of TNF-alpha at P17 by 6.4-fold. At this dose, it also suppressed the baseline TNF-alpha expression in the mouse model. In summary, TNF-alpha is altered in the development of oxygen-induced retinopathy in the mouse. It increased markedly during the vasoproliferative phase and was suppressed by dexamethasone. Modulation of TNF-alpha expression may provide a potential site of action for future therapeutic targets.
Yossuck
P
P
Department of Pediatrics, Division of Neonatology, Georgetown University Children's Medical Center, Washington, DC 20007 , USA.
Yan
Y
Y
Tadesse
M
M
Higgins
R D
RD
D000367:Age Factors; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000378:metabolism; D012160:Retina / Q000187:drug effects; D012162:Retinal Degeneration / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D010100:Oxygen