In the news: Meta-Analyses on Vitamin D in AMD; Brain Involvement in Glaucoma? Alpha Lipoic Protects RGCs in Glaucoma Model

Circulating Vitamin D & AMD Risk: 2 Reviews

A relationship between serum vitamin D [25(OH)D] levels and AMD occurrence was first reported in 2007. Other epidemiologic studies followed, the majority of which found inverse associations between circulating levels of this vitamin and AMD. Recently, two systematic reviews and meta-analyses examining this association have been published.

The first meta-analysis (1), performed by university researchers in China, included 10 studies. The researchers found a non-significant association per 10 ng/mL increase of serum D in this meta-analysis, with no inverse associations seen between serum D levels and stages (early, late, advanced) or subtypes (dry vs. wet) of AMD risk. The authors, however, indicate that opposite results from US and Korean studies accounted for the non-significance, with US studies showing decreasing risk – and Korean studies increasing risk – with higher serum D levels.

In contrast, French researchers found evidence that high serum D concentrations may be protective against AMD, and that concentrations below 50 nmol/L (≈ 20 ng/mL) are associated with late AMD (2). Twenty-one studies met the selection criteria for this meta-analysis and systematic review. AMD was shown to be inversely associated with the highest serum D quintile compared to the lowest quintile (OR=0.83). Notably, those with the highest serum D levels were 53% less likely to develop late AMD.

The observed connection between vitamin D and AMD is biologically plausible: inflammation and angiogenesis are part of the disease process, and vitamin D has both anti-inflammatory and anti-neovascular activity. Well-designed longitudinal studies are needed to better understand the role of vitamin D in different stages and types of AMD.

Glaucoma: Disease of the Eye or Brain Too?

One outstanding issue in glaucoma research is whether glaucoma should be considered an eye disease exclusively, or also a brain disease. Alzheimer’s and glaucoma, for example, share many biological and mechanistic features, and some research suggests an overlap of these neurodegenerative diseases. To further examine this issue, a Dutch and Japanese team used Diffusion Tensor Imaging to study the brain’s white matter integrity in 30 Japanese with normal-tension glaucoma, and age-matched controls (3).

Evidence of neurodegeneration was found in the brain’s occipital lobes (the main centers for visual processing), the forceps major and corpus callosum. In particular, according to the authors, degeneration of the corpus callosum suggests that neurodegeneration is not limited to the primary visual pathways. The findings raise provocative questions: Does a brain component, independent from eye damage, play a role in glaucoma development? Are different mechanisms involved in normal and high pressure glaucoma? Click to view the paper.

α-Lipoic Acid Protects RGCs in Model of Glaucoma

Evidence suggests that oxidative stress worsens neurodegenerative diseases, including glaucoma. In a mouse model of glaucoma (DBA/2), researchers tested the contribution of oxidative stress in glaucoma development (4). They found lipid peroxidation and up-regulation of oxidative stress-related mRNA and protein in the retinas of these animals.

Mice were then fed α-lipoic acid (ALA) starting at age 6 months, to test the role of ALA as an intervention in disease progression. Separately, mice were raised on an ALA-supplemented diet to test its effect on prevention. Both ALA treatment paradigms showed increased antioxidant gene and protein expression and increased protection of retinal ganglion cells (RGCs) compared to controls. Decreased measures of oxidative stress in the retina were seen in both treatments. The authors conclude that ALA reduces oxidative damage and improves RGC survival.

References:

1. Wei Wu, et al. The association between serum vitamin D levels and age-related macular degeneration: A system-atic review and meta-analytic review. Invest Ophthalmol Vis Sci 57:2168-77, 2016.
2. Annweiler C, et al. Circulating vitamin D concentration and age-related macular degeneration: Systematic review and meta-analysis. Maturitas [Epub ahead of print] Apr 2016.
3. Boucard CC, et al. Neurodegeneration beyond the primary visual pathways in a population with a high incidence of normal-pressure glaucoma. Ophthalmic Physiol Opt. 36: 344–53, 2016.
4. Inman DM, et al. α-ipoic acid treatment limits glaucoma-related retinal ganglion cell death and dysfunction. PLoS ONE 8:e65389, 2013.