Abstract
To investigate the neuroprotective effect of brimonidine after retinal ischemia damage on mouse eye. Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss, and high intraocular pressure. Ischemia reperfusion (I/R) injury model was used in C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mouse eyes were treated topically with brimonidine and pattern electroretinogram were used to assess the retinal ganglion cells (RGCs) function. A wide range of inflammatory markers, as well as anti-inflammatory and neurotrophic molecules, were investigated to figure out the potential protective effects of brimonidine in mouse retina. In particular, brain-derived neurotrophic factor (BDNF), IL-6, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor DR-5, TNF-α, GFAP, Iba-1, NOS, IL-1β and IL-10 were assessed in mouse retina that underwent to I/R insult with or without brimonidine treatment. Brimonidine provided remarkable RGCs protection in our paradigm. PERG amplitude values were significantly (p < 0.05) higher in brimonidine-treated eyes in comparison to I/R retinas. Retinal BDNF mRNA levels in the I/R group dropped significantly (p < 0.05) compared to the control group (normal mice); brimonidine treatment counteracted the downregulation of retinal BDNF mRNA in I/R eyes. Retinal inflammatory markers increased significantly (p < 0.05) in the I/R group and brimonidine treatment was able to revert that. The anti-inflammatory IL-10 decreased significantly (p < 0.05) after retinal I/R insult and increased significantly (p < 0.05) in the group treated with brimonidine. In conclusion, brimonidine was effective in preventing loss of function of RGCs and in regulating inflammatory biomarkers elicited by retinal I/R injury.
Highlights
Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss and high intraocular pressure (IOP) (Bucolo and Drago, 2011)
Brimonidine Protects RGCs glaucoma the therapeutic approach could be different, on this regards it is worth of note that anti-VEGF agents, used in clinical practice, such as ranibizumab, bevacizumab and aflibercept are considerably different in terms of molecular interactions when they bind with VEGF (Platania et al, 2015)
No significant changes were observed in terms of latency in all groups (Figure 1D) as expected considering the short time after the injury, whereas the average Pattern electroretinogram (PERG) amplitude of I/R mice was significantly (p < 0.05) reduced compared to the control retina
Summary
Glaucoma is an optic neuropathy characterized by retinal ganglion cells (RGCs) death, irreversible peripheral and central visual field loss and high IOP (Bucolo and Drago, 2011). A Cochrane systematic review (Sena and Lindsley, 2017) showed that one clinical trial found less visual field loss in the brimonidine-treated group, the evidence was of such low certainty that it is not possible draw conclusions from this only finding. A systematic review and metaanalysis concluded that the clinical evidence of neuroprotective effect of brimonidine is inconclusive and needs stronger support maybe with large double-blind randomized clinical trials (Scuteri et al, 2020). To shed light on these controversial studies we aimed to investigate topical brimonidine on a well-known in vivo paradigm of retinal damage. Retinal ischemia–reperfusion (I/R) is an experimental model that triggers an inflammatory process eliciting a large number of detrimental molecules such as TNF, tumor necrosis factor-related apoptosisinducing ligand (TRAIL) and ILs (Osborne et al, 2004; Wei et al, 2011; Dibas et al, 2018)
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