Abstract
Purpose: :
Our previous results indicated that oxygen induced retinopathy (OIR) coincided with retinal damage, inflammation, and activation of microglia that expressed TNF-alpha. It is unclear whether hyperoxia-triggered inflammation is either destructive, or an essential part of healing injured tissue. We hypothesize it is possible to reduce OIR by inhibiting the destructive components of inflammation and/or increasing the wound healing components. In these experiments we examined the role of TNF-alpha in OIR.
Methods: :
OIR was induced in postnatal C57BL/6 mice by delivering 75% oxygen for 5 days (from P7 to P12) followed by room air. Five days later (P17) mice received an intravitreal injection of 10ng of mouse recombinant-TNF-alpha into the left eye. As a negative control, mice received an intravitreal injection of saline. Retinas were examined for: (i) areas of non-perfusion in retinal vasculature, (ii) activation of glia and microglia (via GFAP and Iba1 expression), (iii) apoptosis of retina (via TUNEL staining), and (iv) retinal damage (via H&E staining).
Results: :
In order to determine the influence of TNF-alpha in OIR, mice received either exogenous TNF-alpha treatment, or saline (negative control). TNF-alpha accelerated: (i) abnormal re-perfusion of the retinal vessels at P20 and kept both irregularity of vessel formation and permeability at P24 compared with saline injection. TNF-alpha treatment also coincided with (ii) activation of Muller cells, microglia and increased (iii) apoptosis of retina. There was increased (iv) retinal damage that mediated increased retinal folding and thinning of the inner nuclear layer.
Conclusions: :
Increase of TNF-alpha following hyperoxia significantly enlarged inflammation that accelerated re-perfusion of retinal vessels. However, TNF-alpha also activated glia and microglia that triggered increased retinal damage. These data imply that minimizing inflammation due to hyperoxia may reduce retinal damage and gliosis in OIR.
Keywords: inflammation • oxygen • wound healing