| Summary: | 碩士 === 長庚大學 === 臨床醫學研究所 === 101 === Purpose: Visual loss associated with brain damage is currently the most common cause of visual impairment in children in developed countries. Hypoxic-ischemia (HI) injury is one of the most common causes for those neurological damages. We hypothesized that HI insult in the immature eyes per se may play a significant role in the visual impairment in those children. Vannucci model is one of the most widely used experimental paradigms to induce HI brain injury in rat pups. It remains to be determined the long-term functional and pathological sequalae of retina injury after HI in neonatal rats.
Methods: On P7 rat pups, HI was induced by unilateral common carotid artery ligation followed 1 hour later by 8% oxygen hypoxia for 2 hours. Developmental function alterations of retina were assessed by electroretinography (ERG) at different time points. Retinal injury was assessed by HE, hypoxyprobe staining, and TUNEL. The retinal inflammation and gliosis were evaluated by TNF-α, IgG, ED1 and GFAP immunohistochemical staining. The apoptotic pathways were examined by PARP and caspase 3 cleavage, caspase 8 activation and AIF nuclear translocation using immunoblot and immunofluorescent studies.
Results: We found rapid (3 hours after HI) and extensive severe injury in ganglion cell layer (GCL, 60 % cell lost), inner plexiform layer (IPL, 55 % thickness reduction) and inner nuclear layer (INL, 45 % thickness reduction) in the ipsilateral retina after HI injury. The pathological evidence of retinal injury was corresponding to the marked alteration of retinal maturation, especially the b-waves amplitude, in ERG. HI insult in neonatal rats can cause damage in the immature retina per se, as supported by the significant hypoxic stress in the ganglia cells and prominent apoptosis and gliosis in the GCL and INL. Similar to the neonatal HI brain injury, the retinal cell death is primarily apoptotic, by both caspase-dependent and –independent pathways.
Conclusions: HI induces retinal damage at both pathological and functional level in neonatal rats. Further retino-protectal study is important to attenuate vision loss related with retinal damage that frequently occurs after HI.
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