Characterisation of the Ageing Piebald Virol Glaxo Rat Retina: Effect of hemichannel modulation on the ageing process

Abstract

Background: Vision loss is one of the most prevalent conditions affecting the ageing population. It is estimated that 1 in every 3 elderly people have an age-related vision problem. In the ageing eye, abnormal cell to cell communication and elevated immune system response have been identified as mechanisms that contribute to the ageing process. Studies have shown that expression of connexin hemichannels and increased inflammatory response may underlie ocular pathologies, particularly those that emerge in the ageing eye. The inflammasome pathway, reported to be modulated by connexin43 hemichannel opening, is also a novel mechanism in the ageing process. I have hypothesised that treatment with connexin43 hemichannel blockers will reduce the inflammation process in the ageing eye. To test this hypothesis, I have utilised ageing Piebald Virol Glaxo (PVG) rats and investigated the different molecular pathways that underlie the ageing process. Method: Optical coherence tomography (OCT) and fundus imaging was utilised for detection of retinal structure in 0.5, 1.4 and 2.2 years old male and female PVG rats. Immunohistochemical labelling of inflammatory cells and cell death markers were used. To study the vasculature of the choroid, fundus imaging were processed and quantified. Ageing PVG rats treated with a connexin hemichannel blocker (tonabsersat) given at 0.4 mg and 0.8 mg orally for a total of 95 days was also assessed. Results: OCT scans of the retina showed that the inner plexiform layer and photoreceptor layer differed in thickness between young and old rats. Analysis of the choroid vasculature showed that blood vessel density changes were restricted to the young age group. Oxidative stress was elevated in the old rats. Overall, there were no significant inflammatory changes in the ageing eye, and inflammasome proteins were seen but not formed an active inflammasome. Treatment with a connexin hemichannel modulator did not cause any changes. Conclusion: There were no significant differences in the treated and untreated eyes but there was also no expression of markers of ageing in the retina, despite the advanced animal age and evidence of inflammation in the PVG old rat brain. Thus, more research into the PVG rat model could provide the discovery of novel anti-ageing mechanisms that confer protection to retinal structures and prevents the onset of inflammation in the retina in this rat strain.