Brimonidine is Neuroprotective in Animal Paradigm of Retinal Ganglion Cell Damage

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.

7,8-Dihydroxiflavone Maintains Retinal Functionality and Protects Various Types of RGCs in Adult Rats with Optic Nerve Transection

“…Several strategies have been explored to slow down the loss of RGCS following several types of retinal insults, including the use of alpha two agonists [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ] and the use of substances with neuroprotective properties, such as trophic factors and neurotrophins [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], of which BDNF is the most potent neuroprotectant for the retina [ 30 ], and the caspase inhibitors [ 31 ], among others [ 32 ]. Moreover, different pharmacological approaches have provided new evidence of RGCs protection [ 33 , 34 , 35 ].…”

A Comparison of Hyper-Reflective Retinal Spot Counts in Optical Coherence Tomography Images from Glaucomatous and Healthy Eyes

“…Indeed, previous studies have found a potential pro-inflammatory effect on the retina of topically applied benzalkonium chloride, a preservative commonly used in eye-drops [29]. Moreover, α2-adrenergic agents are known to exert a neuroprotective effect on RGCs in vitro [30,31], in animal models of glaucoma [32,33] and potentially in human subjects affected with normal tension glaucoma [34]. However, the aim of this pilot study was uniquely to investigate the numerosity of HRS in patients affected with glaucoma in comparison to healthy controls, and is underpowered to find differences among patients treated with different topical hypotensive agents.…”

Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies

“…Newer drugs including a conjugate of latanoprost and an NO-donor (latanoprostene bunod, approved 2017; Cavet et al, 2014) Kirihara et al, 2018a;Kirihara et al, 2018b;Fuwa et al, 2018;Fuwa et al, 2021;Ferro Desideri et al, 2019;Aihara et al, 2020a;Aihara et al, 2020b;Sharif et al, 2020) (Figure 9). Interestingly, some drugs like brimonidine and betaxolol, not only lower IOP but are also neuroprotective, at least in animal models of IOPdependent and IOP-independent glaucomatous damage (e.g., Rusciano et al, 2017;Conti et al, 2021).…”

“…Of the drugs that have been clinically evaluated for neuroprotective activity and to retard vision loss or impairment in POAG patients, for example brimonidine and memantine, none have conclusively proven effective thus far (Almasieh and Levin, 2017;Levin, 2017). It is worth noting that a very recent study demonstrated the neuroprotective activity of brimonidine after retinal ischemia (Conti et al, 2021). There is some hope and promise that oral vitamin-B3/ nicotinamide may offord some degree of functional vision preservation in POAG patients (Williams et al, 2017c;Hui et al, 2020).…”