Is There More to Glaucoma Treatment Than Lowering IOP?

doi:10.1016/j.survophthal.2007.08.013

Survey of Ophthalmology

Volume 52, Issue 6, Supplement, November 2007, Pages S174-S179

https://doi.org/10.1016/j.survophthal.2007.08.013 Get rights and content

Abstract

Classic glaucoma treatment focuses on intraocular pressure (IOP) reduction. Better knowledge of the pathogenesis of the disease has opened up new therapeutical approaches. Whereas most of these new avenues of treatment are still in the experimental phase, others, such as magnesium, gingko, salt and fludrocortisone, are already used by some physicians. Blood pressure dips can be avoided by intake of salt or fludrocortisone. Vascular regulation can be improved locally by carbonic anhydrase inhibitors, and systemically with magnesium or with low doses of calcium channel blockers. Experimentally, glaucomatous optic neuropathy can be prevented by inhibition of astrocyte activation, either by blockage of epidermal growth factor receptor or by counteracting endothelin. Glaucomatous optic neuropathy can also be prevented by nitric oxide-2 synthase inhibition. Inhibition of matrix metalloproteinase-9 inhibits apoptosis of retinal ganglion cells and tissue remodeling. Upregulation of heat shock proteins protects the retinal ganglion cells and the optic nerve head. Reduction of oxidative stress especially at the level of mitochondria also seems to be protective. This can be achieved by gingko; dark chocolate; polyphenolic flavonoids occurring in tea, coffee, or red wine; anthocyanosides found in bilberries; as well as by ubiquinone and melatonin.

Section snippets

Inhibition of activation of astrocytes

The activation of the astrocytes in the optic nerve head (ONH) and retina plays an essential role in the pathogenesis of GON.26, 28, 68 Both mechanical and ischemic stress can lead to activation of astrocytes. Once activated, astrocytes upregulate the production of various molecules, including matrix metalloproteinases (MMPs), nitric oxide synthase-2 (NOS-2), tumor necrosis factor-alpha (TNF-α), and endothelin, thereby creating an altered microenvironment leading to tissue remodelling and

Conclusion

Theoretically, a number of options are available to treat glaucoma. The different risk factors known lead through the same or similar pathomechanisms to GON. Therapeutically, we can either eliminate or mitigate risk factors or target defined pathogenic steps. Risk factors that can be influenced include increased IOP, low blood pressure, and vascular dysregulation. Pathogenic steps that can be targeted include activation of astrocytes, upregulation of NOS-2 or MMPs. At the moment any type of

Method of Literature Search

A systematic search of the Medline database using the PubMed Web site (through 2007) was conducted using the following key words: non-IOP lowering treatment, POAG, oxidative stress, reactive oxygen species, astrocytes, epidermal growth factor receptor, tyrosine kinase inhibitor, Endothelin-1, Endothelin blockers, calcium channel blockers, dipyrimadole, nitric oxide synthase-2, aminoguanidine, fludrocortisone, carbonic anhydrase inhibitors, calcium channel blockers, omega-3-fatty acids,

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The therapeutic success of minimal invasive glaucoma surgery (MIGS) is challenging due to many factors including fibrotic or occlusive events. Recent clinical data show sudden peaks of intraocular pressure (IOP) in the postoperative care of glaucoma patients after suprachoroidal draining stents. Yet, the reasons for the IOP peaks are speculative. As a link between trace elements and fibrosis had been previously observed in systemic disorders, the present study aimed to investigate the impact of trace elements on the therapeutic success of the suprachoroidal draining stents in patients with open-angle glaucoma (OAG).
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Levels of Mg were significantly lower one month postoperatively in the success group (LS-Mean 1.30 mg/L) compared to the qualified success group (LS-Mean 1.22 mg/L; p-value = 0.04). Fe was significantly increased in the failure group (LS-Mean 2.07 µg/L) compared to the qualified success group (LS-Mean 1.64 µg/L; p-value = 0.019) after 3 months of follow-up. Additionally, Fe levels were significantly lower in the success group (LS-Mean 1.47 µg/L) compared to the failure cohort (LS-Mean 2.07 µg/L; p-value = 0.009). After a period of 18 months, significantly higher levels of Mn were observed in the success group (LS-Mean 1.24 µg/L) than in the failure group (LS Mean 0.30 µg/L, p-value = 0.019).
The present data might suggest that trace elements can influence therapeutic success of suprachoroidal draining devices postoperatively and thus offer first hints for potential novel therapeutic options.
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ANTIAPOPTOTIC EFFECT OF TAURINE AGAINST NMDA-INDUCED RETINAL EXCITOTOXICITY IN RATS
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Citation Excerpt :
The pathophysiology of glaucoma is currently poorly understood (Agarwal et al., 2009; Ebneter et al., 2011; Casson et al., 2012). The current medical therapy for glaucoma is limited to lowering of intraocular pressure (IOP), as this has been established as the primary risk factor for the initiation and progression of RGC loss and optic neuropathy (Goldblum & Mittag, 2002; Mozaffarieh & Flammer, 2007). However, elevated IOP is only one of the several risk factors that lead to RGC apoptosis.
N-methyl-D-aspartate (NMDA) excitotoxicity has been proposed to mediate apoptosis of retinal ganglion cells (RGCs) in glaucoma. Taurine (TAU) has been shown to have neuroprotective properties, thus we examined anti-apoptotic effect of TAU against retinal damage after NMDA exposure.
Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique.
Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 μm length (by 1.5-fold, p < 0.001) and per 100 μm² area (by 1.41-fold, p < 0.05) of the GCL. After NMDA exposure, visible axonal swelling was observed in optic nerve sections. In comparison with the changes observed in the NMDA treated group, the TAU treated group showed fewer prominent changes; axonal swelling was less frequent and less marked. Additionally, no marked glial cell changes were observed in the TAU-pretreated group. All TAU treated groups, particularly the pre-treated group, showed a significant decrease in the NMDA-induced optic nerve damage, with a 50% reduction (p < 0.001) in the mean grading compared to NMDA group. For the same, there was 25% decrease in co- and post-treatment groups, as compared with the NMDA group. Pre-treatment with TAU abolished apoptotic response to NMDA as indicated by decrease in the number of TUNEL- and caspase-3-positive cells. TAU pre-treatment also increased the Bcl-2 level (by 2.80-fold, p < 0.001) and decreased the level of Bax (by 34%, p < 0.01), and activity of caspase-3 (by 36%, p < 0.001) compared to NMDA group.
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: The authors reported no proprietary or commercial interest in any products mentioned or concepts discussed in this article.

View full text

Is There More to Glaucoma Treatment Than Lowering IOP?

Abstract

Section snippets

Inhibition of activation of astrocytes

Conclusion

Method of Literature Search

J Nutr

J Biol Chem

Surv Ophthalmol

Prog Retin Eye Res

Brain Res

Biochem Biophys Res Commun

Am J Med

J Nutr

Kidney Int

Ophthalmology

Eur J Pharmacol

Med Hypotheses

Pharmacol Res

Prog Retin Eye Res

Free Radic Biol Med

Mitochondrial abnormalities in patients with primary open-angle glaucoma

Invest Ophthalmol Vis Sci

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human optic nerve head astrocytes

Glia

The chemistry of melatonin's interaction with reactive species

J Pineal Res

Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking

Science

Modulation of endothelin-1-induced contractions by magnesium/calcium in porcine ciliary arteries

Graefes Arch Clin Exp Ophthalmol

Effects of EGb 761 Ginkgo biloba extract on mitochondrial function and oxidative stress

Pharmacopsychiatry

Stabilization of mitochondrial membrane potential and improvement of neuronal energy metabolism by Ginkgo biloba extract EGb 761

Ann NY Acad Sci

Increased plasma endothelin-1 levels in patients with progressive open angle glaucoma

Br J Ophthalmol

Vascular relaxation to omega-3 fatty acids: comparison to sodium nitroprusside, nitroglycerin, papaverine, and D600

Cardiovasc Drugs Ther

[Glaucomatous optic neuropathy: a reperfusion injury]

Klin Monatsbl Augenheilkd

Effect of acetazolamide on the differential threshold

Arch Ophthalmol

Reversibility of a glaucomatous visual field defect after acetazolamide therapy

Can J Ophthalmol

Vascular dysregulation: a principal risk factor for glaucomatous damage?

J Glaucoma

Influence of nifedipine on the visual fields of patients with optic-nerve-head diseases

Eur J Ophthalmol

The influence of magnesium on visual field and peripheral vasospasm in glaucoma

Ophthalmologica

Short- and long-term effect of nifedipine on the visual field in patients with presumed vasospasm

J Int Med Res

Relationship between retinal glial cell activation in glaucoma and vascular dysregulation

J Glaucoma

The pathogenesis of optic disc splinter haemorrhages: a new hypothesis

Acta Ophthalmol Scand

Fludrocortisone in the treatment of systemic hypotension in primary open-angle glaucoma patients

Int Ophthalmol