Closed Gateways — Can Neuroprotectants Shield the Retina in Glaucoma?

Abstract

Neuroprotection for glaucoma is a therapeutic approach that aims to prevent optic nerve damage or cell death. An appropriate drug that reaches an adequate concentration across the blood retinal barrier is expected to shield the retina in glaucoma. Several in vitro and in vivo attempts in experimental models indicate the possibility of successful neuroprotection. However, clinical trials might not show the same level of neuroprotection as a result of subtherapeutic concentrations of the drug in the eye. The study by Zhong et al. in this issue of Drugs in R&D could not attribute the observed improvement in visual field indices to any one of the individual active constituents of Erigeron breviscapus (vant.) Hand. Mazz. (EBHM). One of the major constituents of EBHM is scutellarin, which is known to have poor oral bioavailability and an unclear ability to penetrate inside the eye. Therefore, before recognizing EBHM as a neuroprotectant in glaucoma for further clinical studies and practice, its active constituents and their pharmacokinetics (systemic as well as ocular) need to be explored.Neuroprotection as a pharmacological strategy to shield retinal ganglion cell death has been a popular approach adopted by many researchers. Yet, its effectiveness in preventing retinal ganglion cell death and thereby preserving vision in patients with primary open-angle glaucoma has not been demonstrated. [1] Mitochondria are abundant in the unmyelinated part of the retinal ganglion cell axons to meet the higher energy demand for nerve conduction and for the maintenance of optimum neuronal function. [2] Ischemia to the optic nerve head region can cause ganglion cell death at different rates. Therefore, effective intraocular pressure (IOP) control and blocking intracellular death triggers are both viable options. The right pharmacologic agent with a meaningful intraocular penetration would rationalize the neuroprotection strategy in glaucoma.For the last three decades, several attempts have been made to establish a successful neuroprotectant for glaucoma using various in vitro and in vivo models. A comprehensive PubMed search with the MeSH terms ''glaucoma'' and ''neuroprotection'' revealed the following compounds, factors and plant extracts: NMDA receptor antagonists (memantine, dexanabinol), an a2-adrenergic receptor agonist (brimonidine), an a 1 -and b-adrenergic receptor antagonist with a nitric oxide donor (nipradilol), an angiotensin II type 1 receptor blocker (candesartan), a prostaglandin-related compound (tafluprost), calcium channel blockers (nilvadipine and cilnidipine), a sodium channel blocker (phenytoin), a dual COMMENTARY Drugs R D 2010; 10 (2): 93-96