Endocrine Abstracts

Background: Blunt ocular trauma causes commotio retinae, a retinal opacification that accounts for over a third of all retinal injuries. Poor outcomes occur when the macula is affected, which accounts for 1/3 of cases and 3/4 cases in those at high injury risk, causing permanent visual loss due to selective photoreceptor death. This is seen in humans, and reproduced in our animal model, as loss of the outer nuclear layer (ONL) on histological and optical coherence tomography (OCT) images.

Photoreceptor apoptosis may be prevented and visual outcomes improved by manipulation of cell death pathways using neuroprotective agents. Progesterone has well-established neuroprotective effects in various models of CNS injury and there is growing evidence that its pleiotropic actions that interfere with cell death pathways may be extended to ocular trauma.

Methods: The present study aimed to assess the neuroprotective efficacy of progesterone for photoreceptor damage in our experimental model of commotio retinae with respect to histological and functional outcomes. Progesterone was administered intraperitoneally (8 mg/kg bolus dose) immediately after trauma, with subsequent continuous infusion (5 μl/h of 10 μg/μl solution) over a 2-week experimental period via osmotic minipump, aiming to reach supraphysiological plasma progesterone levels, above those seen in pregnant rats, where a neuroprotective effect has been observed.

Results: Progesterone induced significantly greater photoreceptor death (P=0.002), with a more pronounced negative effect apparent at increasing distances from the impact site. ERG findings show an initial enhancement of photoreceptor function after 7 days, but overall deterioration after 14 days (P=0.005).

Discussion: This is the first study to report a differential effect of progesterone after short and longer term end points. Progesterone caused a delayed heightened wave of photoreceptor apoptosis after ocular trauma.

Conclusion: Whether this was a concentration, or dosage duration-dependent effect requires further investigation.