A functional and histological analysis on oxygen sensitivity during the critical period of retina development

Abstract

Purpose : The critical period (CP) in the retina is defined by a peak in programmed neuronal cell death from post-natal (P) days 8-16. In the Inner Nuclear Layer (INL) of the retina, CP ranges from P7-P15. Conversely, CP ranges from P12-P20 in the Outer Nuclear Layer (ONL).The goal of this study was to examine the effects of oxygen administered during CP on vision and retinal morphology in wildtype C57BL/6J (C57) and a congenital murine model of retinitis pigmentosa C3H/HeOuJ (C3H) mice. Because C3H mice are homozygous for the Pde6brd1 mutation, there is a significant stress on the ONL of their retinas, resulting photoreceptor cell death. This study was conducted with the hypothesis that oxygen would alleviate some stress being placed on the mouse retina during CP resulting in improved visual function.

Methods : C57 and C3H mice were exposed to either 75% O₂ (hyperoxia) or 21% O₂ (normoxia) during the critical period from P8-P20. Electroretinograpy (ERG) and Optical coherence tomography (OCT) were performed on day 26 and 27, respectively. In addition, histological examination was done on day 28 to assess the effect of oxygen levels on retinal morphology and vision.

Results : The ERG data showed that the average A and B wave amplitudes were higher in C57 and C3H mice exposed to hyperoxia during the critical period compared to mice raised in ambient air. The OCT measurements indicated that treatment of C57 mice with elevated oxygen resulted in a thicker ONL compared to normoxic controls.

Conclusions : Hyperoxic treatment during the critical period improved visual function and reduced retinal thinning. These effects of hyperoxia were sustained following discontinuance of treatment even in C3H mice that normally exhibit severe retinal degeneration and function by 4 weeks of age. Further experimentation is required to distinguish between direct and indirect effects of oxygen on photoreceptor resilience in various forms of retinopathy, including retinitis pigmentosa.

This is a 2020 ARVO Annual Meeting abstract.