Helicobacter pylori and anterior uveitis

Posted by Master, Doctor Mai Vien Phuong - Gastrointestinal Endoscopy - Department of Medical Examination & Internal Medicine - Vinmec Central Park International General Hospital.

Uveitis is a term used to describe various forms of endophthalmitis involving the urethral tract of the eye. It is classified according to the anatomical location and the time course of the disease. Acute anterior uveitis, also known as iritis or iritis, is an inflammatory disorder of the iris and/or uvea (anterior ciliary body) and anterior chamber lasting no more than 3 months. Medial uveitis or uveitis, including vitritis, is defined as inflammation of the vitreous cells, sometimes with a snow border or inflammatory deposition on the vitreous plane . Posterior uveitis indicates inflammation in the retina and/or choroid. Uveitis is a rare disease that is especially common in young people.

The etiological diagnosis of anterior uveitis can be established in about 60% of cases, while 75% of patients with middle uveitis remain undiagnosed. A specific diagnosis can be established in 78% of patients with posterior uveitis. Uveal infections account for about 20% of these cases. Otasevic et al demonstrated that a high proportion of anti-Hp antibodies were present in the serum of a subgroup of patients with acute anterior uveitis. Some of them are affected by degenerative spondylolisthesis. Unfortunately, the sample tested is too small for any specific conclusions to be drawn.

Kim et al found in 165 subjects that Helicobacter pylori infection was associated with high IOP in anterior uveitis, but did not find a true causal link between Helicobacter pylori infection and ocular glaucoma. . So, uveitis is associated with a multitude of diseases. Many chronic inflammatory diseases are associated with an increased risk of uveitis, eg, rheumatoid arthritis, ankylosing spondylitis, Behcet's disease, Crohn's disease. These diseases can cause other types of uveitis due to inflammation, even if they were not diagnosed as uveitis in the first place.

Disruption of the aqueous humor barrier in uveitis involves cell infiltration, increased protein permeability, and up-regulation of cytokines, such as TNF-α and IL-6, and chemokines, such as MCP-1 and MIP-1. In the aqueous humor and uveal regions, exposure of cells near the water-containing blood barrier to inflammatory cytokines and chemokines may ultimately cause cytotoxicity, leading to apoptosis.
Inflammation is associated with an increase in elevated free radical-induced oxidative stress, which can alter the targets, molecular and cellular pathways that are important for normal tissue homeostasis. Free radical generation in turn activates redox-sensitive transcription factors such as NF-κB, which control the expression of a large number of genes involved in apoptosis, cell growth, survival, differentiation, and immune response.

Changes in NF-κB activity have been implicated in a large number of diseases, including autoimmune diseases, cancer, and inflammatory diseases. NF-κB plays an important role in the regulation of immune and inflammatory responses. Pathogens, oxidants, cytokines, chemokines, and oxidative stress-related growth factors activate specific receptors and induce oxidative stress signaling cascades that lead to NF-κB activation. NF-κB activation is responsible for the expression of many genes encoding cytokines (TNF, IL-1, IL-6), chemokines (MIP-1, MCP-1), adhesion molecules (ICAM, VCAM, E-Selectin), iNOS and Cox-2. Free radicals are important modulators of signaling pathways and can regulate both apoptotic signaling and TNF-activated NF-kappaB transcription. In addition, free radicals can also induce redox changes that inhibit NF-kappaB activation, leading to TNF-activated cell death. Increased levels of free radicals during inflammation may be due to increased oxygen consumption in uveitis or decreased antioxidant protection in the involved tissue. Increased levels of free radicals in ocular cells induce redox imbalance, leading to activation of redox signaling mediators. This in turn activates transcription factors, including NF-κB, with the resulting transcription of inflammatory marker genes.

Decreased circulating vitamin C levels in subjects infected with H. pylori may contribute to the etiology of several diseases associated with antioxidant deficiency. Excessive free radical generation also weakens the tissue's own antioxidant defense system, exacerbating inflammation, producing free radicals, and creating tissue damage in uveitis. This damage increases levels of metallo-protease, which chews up proteins inside and out of cells, leading to tissue damage.
During Hp infection, activated macrophages produce the following proinflammatory cytokines: IL-1, IL-2, IL-6, IL-8 and TNF-α. Most of these cytokines are expressed in the aqueous humor of patients with acute idiopathic anterior uveitis. Thus, the possibility of an autoimmune reaction due to molecular mimicry is possible.
Vitamin C seems to have a particularly important role, in fact, in cells. Accordingly, vitamin C helps protect lipid membranes from peroxidation by recycling vitamin E. This can be related to all the eye diseases we have mentioned, especially in glaucoma. while vitamin C has a direct effect on the ocular trabecular system, which can improve their proteolysis in the lysosomal compartment and restore tissue function. Further studies are needed to demonstrate that Ascorbate or other antioxidant supplements have a significant impact on the progression of the association between eye diseases and HP infection.
Inadequate antioxidant protection or overproduction of free radicals creates oxidative stress, which is believed to play a key role in eye aging and in many inflammatory eye diseases . In any case, it is difficult to understand how Hp infection can be associated with such diverse pathologies. It is possible that this "link" could be to recurrent oxidative damage in circulatory disorders, inflammation, and glaucoma. Helicobacter pylori inflammation and ocular diseases progress through a series of common pathogenic aspects shared by the two entities, despite their different clinical features. Indeed, adequate antioxidant defenses responsible for scavenging free radicals are essential for redox homeostasis and suppression of inflammation. These are variables where, for example, corneal epithelial cells have a strong antioxidant capacity. In contrast, other eye tissues, such as the retina, are poorly equipped with antioxidant defenses and are therefore less able to resist the harmful effects of free radicals. Therefore, antioxidant therapy must prove beneficial for the clinical management of patients with H.

REFERENCES
1. Parsonnet J, Shmuely H, Haggerty T. Stool and oral shedding of Helicobacter pylori from infected healthy adults. JAMA 1999; 282 : 2240–2245. [ PubMed ] [ Google Scholar ]
Sergio Claudio Sacca, MD, Aldo Vagge, Helicobacter pylori Infection and Eye Diseases: A Systematic Review. Medicine (Baltimore). 2014 Dec; 93(28): e216.