Ginkgo biloba: an adjuvant therapy for progressive normal and high tension glaucoma

Abstract

Gingko biloba has been used for hundreds of years to treat various disorders such as asthma, vertigo, fatigue and, tinnitus or circulatory problems. Two of the main extracts are EGb761 and LI 1370. Most pharmacological, toxicological and clinical studies have focused on the neuroprotective value of these two main extracts. Neuroprotection is a rapidly expanding area of research. This area is of particular interest due to the fact that it represents a new avenue of therapy for a frustrating disease that may progress despite optimal treatment. One such disease is glaucoma.Glaucoma leads to the loss of retinal ganglion cells and their axons but also to tissue remodelling which involves both the optic nerve head and the retina. In the retina the astrocytes get activated. In addition, the optic nerve gets thinner and the cells of the lateral geniculate ganglion disappear partially. On average, ocular blood flow (OBF) is reduced in glaucoma patients in various tissues of the eye. Increased intraocular pressure (IOP) is a major risk factor for glaucomatous damage. Nevertheless, there is little doubt that other risk factors besides IOP are involved. One such risk factor is a primary vascular dysregulation (PVD) occurring in patients with a disturbed autoregulation, another risk factor is oxidative stress.

Figure 1

Stabilization of mitochondrial membrane potential. A: In vitro treatment with EGb 761 after H₂O₂ insult improves the reduction of mitochondrial membrane potential in dissociated mouse brain cells. Brain cells were damaged with H₂O₂ (5 mM) for 1 h; then EGb 761 was added for 6 h. B: In vivo treatment with EGb 761 improves the decrease of ATP levels in dissociated brain cells. Treated animals received 100 mg/kg EGb 761 p.o. once daily for 2 weeks. Control animals were treated with placebo (0.9% NaCl solution). ATP levels were measured after a 2 h incubation of dissociated mouse brain cells with 2mM H₂O₂. C: In vivo treatment with EGb761 improves mitochondrial membrane potential of isolated mitochondria after H₂O₂ insult. Treated animals received 100 mg/kg EGb 761 p.o. once daily for 2 weeks. Control animal were treated with placebo (0.9% NaCl solution). Mitochondrial membrane potential was measured after a 2 h incubation with 2 mM H₂O₂. Reproduced with permission from Eckert et al. [12].

Figure 2

Surviving retinal ganglion cells distribution in the retina in a rat model of chronic glaucoma. Three groups of animals: A: control, B: EGb761-treated for 5 months, and C: vehicle-treated. A difference between surviving retinal ganglion cells distribution in eyes with elevated IOP that were treated with EGb 761 and vehicle. Reproduced with permission from Hirooka et al. [71].

Figure 3

The effect of gingko extract (EGb76) on retinal ganglion cells of rats. A: Retinal ganglion cells density in retinas with chronic, moderately elevated IOP. Retinal ganglion cells (RGC) were counted in the peripheral retina, approximately 4.0 mm from the optic disc. The graph depicts the mean±standard deviation of five animals treated with vehicle. A significant difference between retinal ganglion cell densities in eyes with elevated IOP that were treated with EGb 761 and vehicle was evident (p=0.0007). Four groups of animals: 1) Control without treated, 2) eyes with elevated IOP without treated (Operated, none), 3) Control, treated with EGb 761, 4) eyes with elevated IOP, treated ith EGb 761 (Operated, EGb761). B: Retinal ganglion cells lost at 5 months in rat eyes with chronic, moderately elevated IOP. Two groups: 1) Not treated, 2) Treated with EGB761. Reproduced with permission from Hirooka et al. [71].

Figure 4

Improvement in preexisting visual field damage in patients with normal tension glaucoma after treatment with GBE. Patients are divided in two groups according to sequences of treatment. Group A: sequence of treatment: GBE- wash out- placebo. Group B: sequence of treatment: placebo-washout-GBE. GBE=Gingko biloba. Reproduced with permission from Quaranta et al. [82].