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Editors Selection IGR 12-1

Basic Science: Trace Elements in the Aqueous

Claudio Perez
Shan Lin

Comment by Claudio Perez & Shan Lin on:

74802 Levels of aqueous humor trace elements in patients with open-angle glaucoma, Hohberger B; Chaudhri MA; Michalke B et al., Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2018; 45: 150-155


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Glaucoma is an optic neuropathy in which the most validated and treatable risk factor is the elevated intraocular pressure (IOP). Nevertheless, the etiology of glaucoma is multifactorial, with several possible concomitant factors including vascular changes and oxidative stress. Priors studies had suggested that oxidative stress and free radical accumulation may harm the trabecular meshwork resulting in an increased IOP1 and also harm to the retinal ganglion cells, with resultant cell death that leads to optic nerve damage characteristic of glaucoma.2 Data from a population-based study had suggested that body levels of trace metals could be involved in the pathogenesis of glaucoma, specifically that lower blood manganese levels or higher serum mercury and ferritin levels are associated with greater odds of glaucoma.3

Therefore, evaluating levels of trace elements in the aqueous humor of glaucomatous patients should provide further information related to this potential avenue of etiology. The cross-sectional study performed by Hohberger B, et al. evaluated the aqueous humor levels of cadmium, iron, manganese, cobalt, copper and zinc in patients with primary open angle glaucoma (POAG, n=12), pseudoexfoliation glaucoma (PEXG, n=10) and cataract patients as controls (n=11). The authors found significantly higher aqueous humor levels of zinc in POAG and PEXG patients compared to controls. They conclude that zinc may be related to glaucoma pathogenesis in general, as matrix metalloproteinases are zinc-containing enzymes and play a possible role in glaucoma pathogenesis.

Matrix metalloproteinases are zinc-containing enzymes and play a possible role in glaucoma pathogenesis
Also, they found significantly lower aqueous humor levels of iron in PEXG patients compared to POAG and controls. Although this study has some design issues, including the relatively small number of eyes in each group and a high variability of results within each group, the findings are of significant interest and provide an excellent starting point for further investigation.

As with other cross sectional studies, it cannot be concluded that zinc or iron levels are a cause or consequence of glaucoma. For example, increased zinc can block copper absorption and cause iron and copper imbalance, and these are elements essential for neural development and immune system. On the other hand, increased zinc could be a compensation mechanism to increase the neutralization of free radicals that are higher in glaucoma.4,5 Future studies can also concurrently measure element concentrations in the serum as well as the aqueous humor. For example blood-aqueous barrier defects have been described in PEXG,6 and therefore increased levels of elements in aqueous humor could be a reflect of increased elements concentration in blood.

As with other cross sectional studies, it cannot be concluded that zinc or iron levels are a cause or consequence of glaucoma
In conclusion, this study suggests that understanding the concentration changes in trace elements in aqueous humor may lead us to further elucidate glaucoma pathophysiology. It encourages future prospective studies into the role of trace elements in this blinding disease.

References

  1. Izzotti A, Bagnis A, Sacc. SC. The role of oxidative stress in glaucoma. Mutat Res. 2006;612(2):105-114.
  2. Moreno MC, Campanelli J, Sande P, Sánez DA, Keller Sarmiento MI, Rosenstein RE. Retinal oxidative stress induced by high intraocular pressure. Free Radic Biol Med. 2004;37(6):803-812.
  3. Lin SC, Singh K, Lin SC. Association between body levels of trace metals and glaucoma prevalence. JAMA Ophthalmol. 2015;133(10):1155-50.
  4. Cruz KJ, de Oliveira AR, Marreiro Ddo N. Antioxidant role of zinc in diabetes mellitus, World J Diabetes. 2015;6(2):333-337.
  5. Ferreira SM, Lerner SF, Brunzini R, Evelson PA, Llesuy SF. Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol. 2004;137(1):62-9.
  6. Küchle M, Nguyen NX, Hannappel E, Naumann GO. The blood-aqueous barrier in eyes with pseudoexfoliation sindrome. Ophthalmic Res. 1995;27 Suppl 1:136-42.

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