Quantification of Neurotrophic Factor Expression in Human and Canine Glaucomatous and Normal Retinas

Abstract

Purpose: : To quantify the expression of neurotrophic growth factors and their receptors in glaucomatous, and normal human and canine retinas.

Methods: : Human (n=9) and canine (n=10) glaucomatous retinas were collected from patients with clinically diagnosed primary glaucoma and without any evidence of other ocular neuropathies. Normal retinas that did not have evidence of any ocular disease were also collected from each species to serve as a control (Human n=9, Canine n=8). Immunohistochemical analysis for neurotrophic growth factors (BDNF, GDNF, CNTF) and their receptors (TrkB, GFR1α, GFR2α, CNTFα) was performed using permanent staining techniques. Images of each retina were captured in central and peripheral locations, and the percentage of each retina that was immunolabeled was determined using Metamorph image analysis software.

Results: : Significantly decreased GFRα2 immunoreactivity (IR) was detected in human glaucomatous retinas (26.27 ± 3.47%, mean ± SEM) as compared to healthy, control retinas (40.99 ± 5.1%, p = 0.03, Student’s t test). Analysis of the inner plexiform and ganglion cell layers only revealed the same trend, with glaucomatous retinas having significantly less IR than control retinas (22.59 ± 4.97% and 45.49 ± 5.82%, respectively, p = 0.0293). Additionally, we observed a slight elevation of BDNF IR and decrease in the high-affinity BDNF receptor TrkB IR in canine and human glaucomatous retinas (although neither BDNF nor TrkB IR changes were statistically significant). There were no significant changes in CNTF and CNTFα IR between control and glaucomatous eyes.

Conclusions: : This study has systematically examined neurotrophins and their receptors in two species suffering from primary glaucoma. We have demonstrated a decreased expression of GFRα2 in glaucomatous retinas in all retinal layers. Additionally, the increase in BDNF expression in glaucomatous retinas is in stark contrast to previously published data.

Keywords: retina • ganglion cells • neuroprotection