Many studies have found that mercury exposure causes retinal
neurotoxicity involved in many of the common chronic eye conditions (1-4)
Mercury accumulates in
the brain and retina of the eye (1).
Several toxic metals are taken up by the human retina
and optic nerve head. Injury to the retinal pigment epithelium from toxic
metals could damage the neuroprotective functions of the retinal pigment
epithelium and allow toxic metals to enter the outer neural retina. mercury is
taken up preferentially by fetal retinal ganglion cells, optic nerve glial
cells, the retinal pigment epithelium, and endothelial cells. Mercury induces
free radical formation, autoimmunity, and genetic and epigenetic changes, so
these findings raise the possibility that mercury plays a part in the
pathogenesis of degenerative CNS disorders that also affect the retina and
optic nerve. These findings support the hypothesis that accumulations of toxic
metals in the retina could contribute to the pathogenesis of age-related
macular degeneration(1bc).
Inorganic mercury (
Hg(
2+))
is a prevalent environmental contaminant to which exposure can damage rod
photoreceptor cells and compromise scotopic vision(1f). The retinal
pigment epithelium (RPE) likely plays a role in the ocular toxicity associated
with
Hg(
2+) exposure in that it mediates
transport of substances to the photoreceptor cells. In order for
Hg(
2+) to access photoreceptor cells, it must first be taken
up by the RPE, possibly by mechanisms involving transporters of essential
nutrients. In other epithelia,
Hg(
2+), when
conjugated to cysteine (
Cys
)
or homocysteine (
Hcy
), gains access to the
intracellular compartment of the target cells via amino acid and organic anion
transporters. Accordingly, the purpose of the current study was to test the
hypothesis that
Cys
and
Hcy
S-conjugates of
Hg(
2+)
utilize amino acid transporters to gain access into RPE cells. Time- and
temperature-dependence, saturation kinetics, and substrate-specificity of the
transport of Hg(2+), was assessed in ARPE-19 cells exposed to the following
S-conjugates of Hg(2+):
Cys
(
Cys
-S-Hg-S-
Cys
),
Hcy
(
Hcy
-S-Hg-S-
Hcy
), N-acetylcysteine (NAC-S-Hg-S-NAC) or glutathione
(GSH-S-Hg-S-GSH). We discovered that only
Cys
-S-Hg-S-
Cys
and
Hcy
-S-Hg-S-
Hcy
were taken up by these cells. This transport
was
Na(
+)-dependent and was inhibited by neutral
and cationic amino acids. RT-PCR analyses identified systems
B(
0,+) and ASC in ARPE-19 cells. Overall, our data suggest
that
Cys
-S-Hg-S-
Cys
and
Hcy
-S-Hg-S-
Hcyare
taken up into
ARPE-19 cells by Na-dependent amino acid transporters, possibly systems
B(
0,+) and ASC. These amino acid transporters may play a
role in the retinal toxicity observed following exposure to mercury(1f).
A
study of
battery industry workers who had been chronically exposed to
mercury to evaluate the toxic effects of mercury on retinal nerve fiber layer
thickness (RNFLT), macular thickness (MT), and choroidal thickness (CT) by
using spectral-domain optical coherence tomography (SD-OCT) (1e). Battery
factory workers (n=31) and healthy non-factory employee controls (n=15)
participated in the study. Participants were divided into 3 groups: Group 1
(n=15) was factory workers who had worked for more than 5 years in a mercury
battery factory; Group 2 (n=16) was factory worker who had worked for less than
5 years in a mercury battery factory; and Group 3 (n=15) was healthy
non-employees. Systemic symptoms were recorded. Ophthalmic examination included
best-corrected visual acuity test, color vision test, full ophthalmologic
examination, and SD-OCT of the RNLF, macula, and choroid. To determine mercury
exposure, venous blood samples were collected, and mercury levels were
assessed. There were no significant differences between Group 1 and Group 2,
but
there were significant differences between Group 3 and both Group 1 and
Group 2 in best-corrected visual acuity values (1=2<3), color vision scores,
blood mercury levels, and duration (mean ±SD, range) of mercury
exposure(1>2>3). OCT values of RNFLTs, MTs, and CTs of all 3 groups were
statistically different from each another (1e).
The study author
recommends that
SD-OCT can be useful for evaluating the toxic
effects of chronic exposure to mercury.
Chronic
exposure to
metals (inorganic lead, methyl mercury, and mercury vapor) or
organic solvents (carbon disulfide, trichloroethylene, tetrachloroethylene,
styrene, toluene, and mixtures) resulted in toxic substances in the eyes, and
the
toxicants altered color vision, rod- and/or cone-mediated electroretinograms,
visual fields, spatial contrast sensitivity, and/or retinal thickness
. (4)
The toxic metals
lead and cadmium were
found in all of the pigmented ocular tissues studied
,
concentrating to the greatest extent in the retinal pigment epithelium/choroid.
Lead, mercury, cadmium, aluminum, and other
xenobiotic metals are implicated in structural and physiological damage in the
mammalian eye.
Toxic
mechanisms reflect imbalances in trace metals or interaction between xenobiotic
and trace metals through competitive binding key carrier proteins and metabolic
pathways leading to trace metal imbalances and functional impairment.
Alternatively, toxic injuries result through direct cytotoxic action of metal
ions on cell membranes, intercellular communication, (4) RNA and DNA damage,
and mutagenic change.
Heavy
metals have been implicated in the mechanisms of endothelial damage. Influences
of heavy metal ions on diverse cell types have been studied using a variety of
in vitro and in vivo methods. Polymorphonuclear neutrophil granulocytes (PMNs)
have physiological and pathological functions, including the modulation of
adhesion to and destruction of endothelial cells (ECs). The initiation of
these important pathogenetic mechanisms of inflammation at very low
metal ion concentrations.
The changes in receptor potential seen are consistent with
mercury inhibiting the rod phosphodiesterase, and with lead having an action in
addition to phosphodiesterase inhibition light sensitivity
Lead and mercury have been
reported to alter selectively the rod component of the electroretinogram,
and to inhibit the
phosphodiesterasein
rod outer
segments which may be responsible for generating the rods' light response. (5b)
The authors have investigated the effect of lead and mercury on the voltage
response to light of
rods, and
compared these effects
with those of the phosphodiesterase inhibitor papaverine. Lead
and mercury, like papaverine, slow the light response. In
addition, papaverine increases the light response amplitude while
lead decreases it.
Mer
cury initially increases and then decreases
the amplitude. (5) The late decrease in amplitude “produced by
mercury
is associated
with rod
degeneration”: an effect which may mimic degenerative diseases in
which the rod phosphodiesterase is insufficiently active. These
results demonstrate that the changes of electroretinogram induced by
lead and mercury can be accounted for by the changes in receptor potential
these heavy metals produce. The changes in receptor potential seen are
consistent with mercury inhibiting the rod phosphodiesterase, and with
lead having an action in addition to phosphodiesterase inhibition.
Recent research shows that occupational exposure to several
solvents, metals and other industrial chemicals can impair color vision in
exposed workers. (6a)
Occupation-related color vision
impairment is correlated to exposure levels and has often been observed in
workers exposed to environmental concentrations below the current occupational
limit proposed by the ACGIH.
Acquired
color vision impairment has been seen related to occupational exposure to
styrene, perchloroethylene (PCE), toluene, carbon disulfide, n-hexane, solvent
mixtures, mercury
. (6)
Another study found reduced contrast
sensitivity at all spatial frequencies was associated with hair Hg
,
while %EPA, and to a lesser extent %EPA+DHA, were associated with
better
visual function
(6c)
10 types of drugs in current use believed to induce cataracts are identified and the evidence of their role is presented. (7a)
Inorganic mercury,
and
the phenothiazines
have all been associated with cataract formation
.
Cataract disease results from non-amyloid
aggregation of eye lens proteins and is the leading cause of blindness in the
world.
Another study reveals that
mercury
ions can induce the aggregation of human lens proteins
, uncovering a
potential role of this heavy metal ion in the bioinorganic chemistry of
cataract disease. (7b)
[Lower plasma Se (P-Se; < 25th percentile, 110 microg/L) and higher blood Hg (B-Hg; > 7c-or = 25th percentile, 25 microg/L) were associated with a higher prevalence odds ratio (POR) of ARC [adjusted POR (95% confidence interval), 2.69 (1.11-6.56) and 4.45 ( 1.43-13.83), respectively]
Near visual acuity was negatively associated with hair Hg and positively associated with %DHA, with a highly significant Log Hg × age interaction term for those aged ≥40 years, clinical presbyopia was associated with hair Hg ≥ 15 μg /g (OR = 3·93, 95% CI 1·25, 14·18) and %DHA (OR = 0·37, 95% CI 0·11, 1·11). (7d)
SEAFOOD/CATARACTS Methylmercury in seafood
may cause lens clouding, contributing to cataract development. Optometrist Ben
Lane noted that his cataract patients liked seafood, while those who didn't
like fish were clear-eyed. A study of 17 patients revealed that the cataract
patients had eaten
salt water
fish or shellfish at
least once a week on the average, but those cataract-free reported using these
foods an average of once every five weeks. The cataract patients showed far
higher concentrations of mercury in their hair. Dr. Lane's study showed that the
presence of 2.3 ppm or more of mercury in hair samples was related to
a 23-fold increase in the risk of cataracts. Dr. Lane encourages his patients
to eat such foods as garlic and pectin-rich foods such as apples to help remove
the mercury, and to receive adequate, while avoiding excessive, amounts of
vitamins A, C, and E. (7e)
Antioxidant eye drops (n-
acetylcarnosine
) have been documented to prevent and
sometimes reverse cataracts (such as Can C drops). [After being diagnosed
with Fuchs Dystrophy (aggressive form of cataracts) more than 35 years ago, I
have improved my eyesight by amalgam replacement, detoxification, and use of
Can C drops since that time (BW).]
Thousands have been documented to have recovered or improved from
chronic eye conditions due to mercury or toxic poisoning after dental metal
replacement and/or detoxification or use of antioxidants. (8)
Toxic metal levels have been shown to be significantly correlated with blood pressure . Glaucoma is an optic neuropathy with multifactor etiology, which affects the optic nerve head (ONH), provoking visual field loss and permanent impairment of visual function (9). There is considerable evidence documenting an impairment of the ocular blood flow, involved both in the onset and progression of the disease. Treatments to reduce Intraoccularpressure IOP are standard. (9cd) A South Korean study (9b) found that toxic metal blood levels are significantly associated with BP and IOP. Additionally, several IOP-independent factors such as glutamate toxicity, oxidative stress, autoimmunity, and vascular dysregulation have been suggested in the pathogenesis of NTG. The IOP reduction remains the main strategy to reduce the damage progression in NTG, but neuroprotection treatments to reduce these other factors should also be considered. (9c) The concept of neuroprotection is based upon increasing evidence that glaucoma degeneration is analogous with other neurodegenerative diseases of the central nervous system suggesting a strong relation between the basic cellular processes in glaucoma and Alzheimer's disease. (9de) Neuroprotection intervention is aimed at neutralizing some of the effects of the nerve-derived toxic factors by increasing the ability of the remaining neurons to cope with stressful conditions. For those with toxic metal exposure which is common and known to cause all the factors discussed here, detoxification is known to reduce blood pressure, and in most cases IOP and these other factors discussed. High dose vitamin C as part of such treatment has been suggested as beneficial, and there is evidence that Hemp CBD (& marijuana) lower IOP (CBD safer option,9g) and Chinese herbs such as Gingko biloba improve blood flow to the optic nerve. There is evidence that detoxification as suggested here has proven to be effective in reducing IOP and reducing other adverse effects in some animal study models (9f).
Some studies found that mercury level was significantly associated with retinitis pigmentosa (10bcd). Notice the relationship to zinc which also is a factor . Retinitis pigmentosa (RP), a neurodegenerative disorder, can arise from single point mutations in rhodopsin, leading to a cascade of protein instability, misfolding, aggregation, rod cell death, retinal degeneration, and ultimately blindness. (10a) Divalent cations, such as zinc and copper, have allosteric effects on misfolded aggregates of comparable neurodegenerative disorders including Alzheimer disease, prion diseases, and ALS. We report that two structurally conserved low-affinity zinc coordination motifs, located among a cluster of RP mutations in the intradiscal loop region, mediate dose-dependent rhodopsin destabilization. Disruption of native interactions involving histidines 100 and 195, through site-directed mutagenesis or exogenous zinc coordination, results in significant loss of receptor stability. Furthermore, chelation with EDTA stabilizes the structure of both wild-type rhodopsin and the most prevalent rhodopsin RP mutation, P( 23)H. These interactions suggest that homeostatic regulation of trace metal concentrations in the rod outer segment of the retina may be important both physiologically and for an important cluster of RP mutations. (9a) Thus proper chelation methods can be used beneficially for either mercury exposure eye damage or epigenetic forms with zinc related destabilization, with periodic tests to monitor ongoing results for progress. For more information on treatment and therapy options for retina pigmentosa see 10efgh.
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