Chelsea Guymer, Glyn Chidlow, John Wood1, Robert Casson
Purpose: To determine; (i) whether the retinal level of pyruvate diminishes during the early stages of glaucoma and can be restored with oral pyruvate, and (ii) whether oral pyruvate supplementation pro- tects against retinal ganglion cell death in an acute experimental animal model of glaucoma.
Method: Sprague Dawley rats (Part 1 n = 24, Part 2 n = 40) were randomly assigned into control and high dose pyruvate supplementation (500mg/kg/ day) groups. In part 1, the rats were humanely killed on day 3 (n = 12) and day 7 (n = 12) and the retinas dissected for analysis. In part 2, experimental glaucoma (laser photocoagulation of the trabecular meshwork and episcleral veins) was induced at day
0. Intraocular pressure was monitored and all rats were terminally anaesthetised on day 14. Spectral domain optical coherence tomography (SD-OCT) was performed on day 0 and day 14.For pyruvate quantiftcation whole retinas were homogenised and the pyruvate level measured. Ret- ina and optic nerves were processed for quantiftca- tion of the number of surviving axons. SD-OCT permits sampling of any real-time morphological changes in the retina and enables correlation of these ftndings with histopathological and immuno- histochemical examinations.
Results: In glaucomatous rats, pyruvate in the drinking water reduces any decline in the normal retinal level of pyruvate to protect against retinal ganglion cell death and thus visual loss in glaucoma.
Conclusion: Given that pyruvate supplementation demonstrates considerable neuroprotection in exper- imental murine glaucoma, this provides a sound pre-clinical evidence base for translation to human trials.