In the news: Gut Microflora & AMD Risk; Ginkgo biloba & Oxidative Stress in Glaucoma

Can Gut Microflora Affect AMD Development?

One of the most rapidly expanding scientific fields of inquiry is that of the human microbiome and its potential influence on many aspects of human health. According to a series of intriguing experiments conducted by University of Montreal researchers, bacterial communities in the gut may even affect the evolution of AMD.

Epidemiological data suggests that the second most important environmental risk factor for men’s progression to neo-vascular AMD (the first being smoking) is abdominal obesity (1). However, the mechanisms underlying this observation remain poorly defined.

Since it is known that high-fat diets can impact intestinal flora, the researchers used mouse models of neo-vascular AMD, microbiotal transplants, and other gut flora-altering methods to uncouple weight gain from confounding factors. This allowed them to determine whether high fat diets worsen choroidal neovascularization (CNV) by altering gut microbiota. They found that fat-rich diets alter the gut micro-biome and in turn elevate choroidal and systemic inflammation and heighten pathological CNV.

In one of the experiments, fecal transplants were used to transfer the microbiota of mice fed regular-fat diets to mice receiving high-fat diets. The fecal transfer restored microbial proportions found in the normal fat diet group to the high-fat fed animals. While mice in the high-fat group showed about a two-fold increase in CNV compared to the regular-fat group, the fecal transfer diminished CNV by ~35% and lessened intestinal permeability. The researchers speculate that altered gut permeability caused by microbial imbalance allows entry of pro-inflammatory signaling molecules. These molecules are produced by intestinal bacteria and induce low-grade systemic inflammation.

“Our study suggests that gut microbiota influences development of neovascular lesions associated with AMD, particularly when obesity is a predisposing factor” (2), wrote the authors. Can modifying microbiota in humans through diet and/or pre- and probiotics reduce systemic and local choroidal inflammation, reduce neovascularization, and help prevent or stall exudative AMD?

Ginkgo May Reduce DNA Breaks in Glaucoma

While elevated IOP is a major risk factor for glaucoma, increasing evidence suggests that disease development is also linked to other factors, such as disturbed ocular blood flow and oxidative stress (3). Unstable ocular blood flow is thought to enhance oxidative stress. Oxidative stress may be an important cause of increased IOP by triggering trabecular meshwork degeneration, as well as causing retinal ganglion cell damage. One measure of oxidative stress is the quantification of DNA breaks by comet assay. Increased DNA breaks in trabecular meshwork and circulating leukocytes have been reported in glaucoma.

Researchers from the Dept. of Ophthalmology at Bern University conducted a retrospective clinical study to quantify single-stranded DNA breaks in circulating leukocytes of bilateral open-angle glaucoma patients (n= 60). These patients were treated for at least 6 months with a) 5 mg of Nifedipine daily; b) 120 mg of Ginkgo biloba daily; or c) no systemic treatment. The study’s aim was to assess whether systemic oxidative stress could be lowered by treatment with Ginkgo (shown to be reduced in vitro), or with a low-dose calcium channel-blocker (Nifedipine), which improves blood flow regulation by inhibiting effects of endothelin-1.

Patients treated with Ginkgo biloba and Nifedipine had a significantly lower amount of comet tails indicative of DNA damage compared with control leukocytes of untreated patients (p < 0.001). Ginkgo biloba exhibited a trend toward having a stronger effect in lowering DNA breaks compared with Nifedipine (p = 0.052). While retrospective studies have inherent limitations, these findings merit prospective investigation.

References

1. Adams MKM, et al. Abdominal obesity and age-related macular degeneration. Am J Epidemiol 173:1246-55, 2011.
2. Andriessen E, et al. Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization. EMBO Mol Med 8:1366-79, 2016.
3. Fang L, et al. The effect of Ginkgo biloba and Nifedipine on DNA breaks in circulating leukocytes of glaucoma patients. Expert Rev Ophthalmol 10:313-18, 2015.