The role and mechanism of retinal ganglion cell death in glaucomatous injury

Purpose Glaucoma refers to a group of diseases characterised by visual field damage and optic neuropathy. In glaucoma, retinal ganglion cell (RGC) death halts the progression of visual information from the eye to the brain, causing permanent visual loss. Due to their crucial role in the pathophysiology of glaucomatous injury, strategies delaying or preventing RGC death are being increasingly recognised as important to incorporate into novel approaches to glaucoma. However, the successful development of such therapies is reliant upon a comprehensive understanding of the mechanisms underlying RGC dysfunction. This study aims to help elucidate this by examining the difference between RGC layer nuclei counts, inner plexiform layer (IPL) thickness, and TrkB signalling in the retina between control and glaucoma human samples. Methods Nine healthy and eight glaucomatous retinas were obtained from the Mayo Clinic, US. 2‐3mm explants from peripheral and central regions were probed for p‐TrkB via immunohistochemistry. Six images per retinal section were quantified for TrkB signalling using ImageJ. RGC layer nuclei counts and IPL thickness measurements were taken as evidence of glaucomatous damage. Results There was a loss of nuclei in the RGC layer, a decrease in IPL thickness, and loss of p‐TrkB signalling in the peripheral human glaucoma samples compared to controls. These changes correlated with a loss of visual field information. No significant changes were observed in the central retina. Conclusions Our findings support the observation that patients lose peripheral vision early in glaucoma. This convincingly supports a picture of RGC death disrupting the transmission of visual information from the peripheral retina in glaucoma patients. Reduced TrkB signalling in glaucoma also demonstrates the importance of this signalling pathway in maintaining RGC survival. Investigating ways to restore, or preserve, TrkB phosphorylation may be beneficial in the treatment of glaucoma.