The Contribution of Fluoride to the Pathogenesis of Eye Diseases: Molecular Mechanisms and Implications for Public Health

Abstract

This study provides diverse lines of evidence demonstrating that fluoride (F) exposure contributes to degenerative eye diseases by stimulating or inhibiting biological pathways associated with the pathogenesis of cataract, age-related macular degeneration and glaucoma. As elucidated in this study, F exerts this effect by inhibiting enolase, τ-crystallin, Hsp40, Na+, K+-ATPase, Nrf2, γ -GCS, HO-1 Bcl-2, FoxO1, SOD, PON-1 and glutathione activity, and upregulating NF-κB, IL-6, AGEs, HsP27 and Hsp70 expression. Moreover, F exposure leads to enhanced oxidative stress and impaired antioxidant activity. Based on the evidence presented in this study, it can be concluded that F exposure may be added to the list of identifiable risk factors associated with pathogenesis of degenerative eye diseases. The broader impact of these findings suggests that reducing F intake may lead to an overall reduction in the modifiable risk factors associated with degenerative eye diseases. Further studies are required to examine this association and determine differences in prevalence rates amongst fluoridated and non-fluoridated communities, taking into consideration other dietary sources of F such as tea. Finally, the findings of this study elucidate molecular pathways associated with F exposure that may suggest a possible association between F exposure and other inflammatory diseases. Further studies are also warranted to examine these associations.

Eye–Hand Coordination Impairment in Glaucoma Patients

“…Glaucoma is clinically defined as progressive damage to the optic nerve and visual field (VF) loss principally associated with a loss of retinal ganglion cells and is widely reported as a leading cause of irreversible visual impairment and blindness [1,2]. Increased intraocular pressure is a major risk factor for glaucoma [3].…”

Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na+, K+-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health

“…Past studies have further suggested that inhibitors of NKA may also contribute to disorders associated with loss of NKA activity [18]. This hypothesis is supported by two current studies which infer a causal association between F − exposure and pathophysiological states associated with loss of NKA activity including iodine deficiency [110] and degenerative eye diseases [53]. Among the many molecular mechanisms identified in these latter studies was the contribution of F − to loss of NKA activity.…”

“…Past studies have also shown that reduced NKA activity may underlie the pathophysiological aspects linked to the prehypertensive status in humans [40,545]. Additionally, it has been widely documented that inhibition of NKA activity is associated with hypertension [44,45,46,47,48,49,50,51,52,53]. Again, several human studies have found that exposure to excessive F is closely associated with hypertension [546,547,548,549,550].…”

“…In addition, loss of NKA activity is also associated with rheumatoid arthritis [30,31], metabolic syndrome [32], including; chronic kidney disease [33,34,35]; diabetes mellitus [36,37]; diabetic nephropathy and cardiomyopathy [38,39,40]; cardiovascular complications [32,41,42,43]; hypertension [40,44,45,46,47,48,49,50,51,52] and obesity [11]. Loss of NKA activity is also implicated in degenerative eye diseases including cataract formation and age related macular degeneration [53]. In addition to inflammatory disorders as noted previously, loss of NKA activity has been found to be associated with tumour invasiveness, metastasis, and tissue fibrosis [54], kidney cancer [54], prostate cancer [55], bladder cancer [56] and urothelial cancer [57].…”

Molecular Hydrogen Attenuated N-methyl-N-Nitrosourea Induced Corneal Endothelial Injury by Upregulating Anti-Apoptotic Pathway

“…The medium containing H 2 and the blank medium were added into 96-well plates, respectively. The media were mixed with 10 μl cell counting kit 8 (CCK-8) solution (Dojindo, Japan) at different time points (2,4,6,12,24,36, and 48 hours) and incubated for 2 hours. The absorbance at 450 nm was determined by Imark enzyme labeling instrument (Bio-Rad).…”