Abstract
Purpose: :
Visual loss associated with brain damage is now the most common cause of visual impairment in children. At present, the single most common cause of visually impaired brain injury in children is perinatal hypoxic- ischemia. The ocular abnormalities and visual dysfunction associated with hypoxic-ischemia injury were found in these patients. The hypoxia-ischemia insult affecting the optic radiation has now become the principal cause of visual impairment and dysfunction in children born prematurely. However, the eye is susceptible to hypoxia ischemic damage in utero and the optic radiation damage was not the only cause of visual dysfunction. We hypothesize that hypoxic ischemic insult in the immature eyes may play a significant role in the visual impairment of these brain damaged children.
Methods: :
Hypoxia- ischemia (HI) eye injury was produced in postnatal day 7 (P7) rats by right common carotid artery ligation followed by hypoxia with 8% O2 for 2hrs. After HI 24 hrs (P8), 48 hrs (P9), 72 hrs (P11), 7 days (P14), 14 days (P21) and 21 days (P33), we evaluate the histological changes in eyes and brains by H&E stain. At the same time, immunohistochemistry staining including hypoxyprobe, TUNEL and cleaved caspase-3 for these eyes slides was performed to explore the possible mechanisms in this model. Functional assessment was done from P14 due to lid fissure opening in this period of time by electroretinography (ERG). Pancaspase inhibitor-VAD intraperitoneal injection was performed after HI 1 hour in P7 and the eyes were analyzed in P14.
Results: :
After HI in P7, hypoxyprobe staining showed increased density in the ipsilateral retinas. A marked reduction in inner retinal thickenss was observed from P8 to P33, and ERG recorded the amplitude of b wave were significant lower in ipsilateral eyes, comparing with contralateral or naïve eyes. TUNEL positive cells increasing from P8 to P9 then dramatic decreasing from P14 to P21 and activated caspase-3 staining showed the same temporal profile. However, i.p VAD only provided moderate but not complete protection from hypoxic-ischemia in immature retinas
Conclusions: :
Theses results indicated HI caused significant retinal damage in immature eyes. The HI model may provide another method to understand the mechanism about the HI induced immature eyes injury and further treatment will be studied for rescuing eyes in these immature infants.
Keywords: inner retina dysfunction: biochemistry and cell biology • pathology: experimental • VEI