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T. Chan-Ling, S. Bisti, R. Maccarone, S. Yun; Rationale for Non-Invasive Treatment of ROP: Dark Rearing Minimises Vaso-Obliteration During Hyperoxia and Mimics Physiological Vascularisation. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3121.
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The initiating event in the pathogenesis of ROP is a hyperoxia-induced regression of the retinal vasculature via the down regulation of VEGF. Preventing this could preclude the onset of ROP. We set out to test our hypothesis that dark rearing minimises vaso-obliteration of retinal vessels during hyperoxia. We suggest that neonates in a high oxygen environment should be subject to total darkness as it causes a metabolic sump through the depolarisation of photoreceptors. When returned to room air the room should be lit, so that the oxygen demand is minimised. We sought to investigate the effect of dark rearing on retinal blood vessels during various stages of experimental ROP, in terms of vessel density, character and stability.
Sprague-Dawley rat pups were raised in the dark under hyperoxic conditions (60% and 75% oxygen) from P0-P4 and placed in room air from P4-P8, to mimic conditions known to cause hyperoxia-induced vaso-obliteration. Blood vessel density was calculated following GS lectin-HRP immunohistochemistry (Chang et al. 2007). The effect of hyperoxia on retinal vessel stability was examined using immunohistochemistry with antibodies to SMA, GS lectin, NG2, CD39 and S100.
The retina of dark reared rats raised in room air had significantly greater density of blood vessels when compared to controls of the same age (39.4±4.2 vs. 50.8±2.4, p0.05, two-tailed student t-test). In contrast, when dark rearing was combined with 75% oxygen, oxygen flux from the arterial oxygen tension exceeded the increased metabolic demands from photoreceptor depolarisation, resulting in significant vaso-obliteration (33.8±1.6, p<0.05). When neonates returned to room air, dark reared and 60% hyperoxia retina showed near normal mural cell ensheathment whereas at 75% oxygen, abnormal preretinal neovascular formations were seen.
These findings are suggestive that dark rearing prevents the vaso-obliteration of retinal vessels induced by oxygen treatment, thus precluding the initiation of ROP. When combined with hyperoxic conditions, there was a mimicking of physiological growth, in terms of vessel density and mural cell ensheathment. Given the non-invasive and cost-effective nature of our treatment, a successful application of dark rearing would have an enormous benefit on public health.
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