Retinopathy of prematurity (ROP) is a potentially blinding retinal disorder, which results from the exposure of the premature infant to hyperoxia. The diagnosis and the assessment of severity of ROP are based on the degree of retinal vascular abnormalities (such as avascular peripheral retina and neovascularisation), which are observed upon fundus examination. However, even if the vascular consequences of ROP are resolved, functional sequels such as high myopia, anisometropia and strabismus, may persist through adulthood. In severe cases, even more dramatic consequences, namely retinal detachment and blindness, may also occur. In oxygen-induced retinopathy (OIR), the animal model of ROP, hyperoxia-induced vasoobliteration and neovascularisation have been studied extensively in mice, rats, cats and dogs. However, the functional and ultrastructural changes that might result from the exposure to hyperoxia have not yet been examined in details. In this study, we report functional, as assessed with the electroretinogram (ERG), and structural, determined with histological sections of the retina, consequences of postnatal hyperoxia which took place during a period of intense retinal maturation, that is, the first 14 days of life of Sprague Dawley rats. / Our results indicate that there is a sigmoidal dose-response correlation between the increasingly longer duration of oxygen exposure, and the decrease in the postreceptoral retinal activity, as revealed by the gradual reduction in the amplitudes of rod and cone dominated b-waves and oscillatory potentials. Furthermore, the cone function appeared to be slightly more affected than that of the rod. Also, of all the ERG components the oscillatory potentials, especially the short latency ones, appeared to be the most sensitive to the hyperoxia. The gradual thinning of the outer plexiform layer (OPL) is also correlated with the duration of oxygen exposure, while the reduction in the number of horizontal cells is not. / Secondly, our experimental approach has allowed us to evidence a period of higher oxygen susceptibility (a window), which takes place during the second week of life of the newborn rats, more specifically around postnatal day 10. Several oxygen exposures of short duration, which included this period, were shown to be more detrimental to the rod and cone function than longer exposures taking place prior to or after this window. This would suggest that during the normal maturation process, the immature retina is not equally sensitive to the hyperoxic insult, presumably because specific retinal structures (synapses in OPL) are targeted by oxygen. / Finally, Trolox C, a potent water-soluble antioxidant, partially prevents the functional and structural consequences of OIR. The prophylactic effect appears to benefit more the rod function than that of the cone. / To conclude, we believe that this new knowledge will help us understand the pathophysiological processes at the origin of oxygen toxicity in the immature retina, thus, significantly increasing our insights on the human form of this disease, namely ROP, which as a result, will be instrumental in devising new therapeutic avenues to help fight this potentially debilitating retinal disorder.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.36907 |
| Date | January 2001 |
| Creators | Dembinska-Knypinski, Olga. |
| Contributors | Lachapelle, Pierre (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Neuroscience.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001802985, proquestno: NQ70000, Theses scanned by UMI/ProQuest. |
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