**7. Selective beta receptor blockade**

Beta blockers have a long history of use in reducing the IOP in glaucoma by reducing the production of aqueous humour. Levobetaxolol, timolol and metipranolol have been shown to have secondary neuroprotective effect by reducing sodium and calcium influx, which reduces the release of glutamate with levobetaxolol being more effective than timolol [50,51,52].

#### **7.1. Betaxolol**

Betaxolol has been shown to reduce the spontaneous firing rate by suppressing glutamategated current and in effect Na currents in the ganglion cells [52]. By doing this it also reversibly blocks the voltage gated calcium current. High intracellular calcium can be neurotoxic. Due to the Ca2+ channel blockage activity by the selective beta 1 beta blocker, betaxolol exerts a neuroprotective effect on the retinal ganglion cells. This effect can be seen at 2-50uM concen‐ tration [53]. Timolol is not effective even in higher concentrations (100uM) and clinically betaxolol is more efficacious in preserving visual fields in glaucoma patients compared to timolol [54]. It has been demonstrated in human cryopreserved retinal arterioles that intralu‐ minal bextaolol caused a significant greater dilatation than timolol, this may be due to the selective nature of the beta blocker [55]

**NEUROPROTECTION STRATEGIES**

• NMDA receptors

**Inhibitors**

**Nitric Oxide Synthase**

Neurotrophic factors (BDNF and CNTF)

Reactive Oxygen species

Immunmodulators Anti Inflammatory agents

TNF- α Inhibitors

Gene Therapy

release

Apoptosis Inhibitors Inhibition of cytochrome c

Caspase inhibitors

(Mitochondrial Augmentation)

**Hypo perfusion** Gingko Bilboa

**Table 1.** Pharmacological neuroprotection strategies

Antioxidants:

scavengers

Glutamate Receptor Antagonists

**Prostaglandin analogue** Latanoprost acid

Memantine Eliprodil

(experimental)

**Beta blockade** Selective Beta Blockade (Betaxolol) Reduces IOP

**Alpha adrenergic agonists** Alpha 2 agonist (Brimonidine) Reduces IOP

Bimatoprost acid Tafluprost acid

**Carbonic Anhydrase Inhibitor** Dorzolamide Reduces IOP

Melatonin Vitamin E Co Q10 cofactor

Ethanrecept

Deprenyl BIRC4

Brain Derived Neurotrophic Factor Ciliary Derived Neurotrophic Factor

Manganese Tetrakis (in vitro)

Cop-1(glatiramer acetate)

IOP lowering medications

Agmatine, an aminoguanidine Aspaminergic agent GLC756

Combinations of nitric oxide donating prostaglandin F2 agonist and with a carbonic anhydrase inhibitor

**Substances studied General Method of Action**

Reduces glutamate excitotoxicity and

Strategies for Neuroprotection in Glaucoma http://dx.doi.org/10.5772/53776 211

neurotoxicity

Reduce oxidative stress

Reduce glutamate production

Reduce glutamate production

Inhibition of COX-2 activity Possible caspase 3 inhibition

suppress the intrinsic apoptosis whilst activating the survival signals

Immunization can modulate immune

Increase mitochondrial expression of bcl-2 and bcl-x, suppresses bax. Improved neuronal survival

activates anti oxidative enzymes Neutralizes free radicals. Oxidative stress can damage the trabecular meshwork, optic nerve head

Upregulates BDNF Calcium channel blockade

Upregulates BDNF Calcium channel blockade Increases anti apoptotic genes

Reduces apoptosis

and retina.

function

including bcl-2

Improved blood flow

Cycloheximide (CHX) inducing neuroprotective genes

Reduces IOP

Betaxolol 0.5% also upregulates the neurotrophic factor BDNF in retinal glia cells [56]. By its action on vascular smooth muscle relaxation this improves blood flow and reduces ischemia induced RGC apoptosis [52, 57]. Retinal ganglion cells protection has been shown using rat experimental model and the preservation of the a and b waves in the electroretinogram in both ischemic-reperfusion and glutamate toxicity models [56,57,58]. This has also been seen in light response experiments on tiger salamander flat mounted retinas [53].
