Trends in Genetics,
Journal Year:
2023,
Volume and Issue:
40(3), P. 228 - 237
Published: Dec. 30, 2023
Age-related
hearing
loss
(ARHL)
is
a
prevalent
concern
in
the
elderly
population.
Recent
genome-wide
and
phenome-wide
association
studies
(GWASs
PheWASs)
have
delved
into
identification
of
causative
variants
understanding
pleiotropy,
highlighting
polygenic
intricacies
this
complex
condition.
While
recent
large-scale
GWASs
pinpointed
significant
SNPs
risk
associated
with
ARHL,
detailed
mechanisms,
encompassing
both
genetic
epigenetic
modifications,
remain
to
be
fully
elucidated.
This
review
presents
latest
advances
studies,
integrating
findings
from
human
model
organisms.
By
juxtaposing
historical
perspectives
contemporary
genomics,
we
aim
catalyze
innovative
research
foster
development
novel
therapeutic
strategies
for
ARHL.
Science Translational Medicine,
Journal Year:
2023,
Volume and Issue:
15(702)
Published: June 28, 2023
Inner
ear
gene
therapy
has
recently
effectively
restored
hearing
in
neonatal
mice,
but
it
is
complicated
adulthood
by
the
structural
inaccessibility
of
cochlea,
which
embedded
within
temporal
bone.
Alternative
delivery
routes
may
advance
auditory
research
and
also
prove
useful
when
translated
to
humans
with
progressive
genetic-mediated
loss.
Cerebrospinal
fluid
flow
via
glymphatic
system
emerging
as
a
new
approach
for
brain-wide
drug
rodents
well
humans.
The
cerebrospinal
inner
are
connected
bony
channel
called
cochlear
aqueduct,
previous
studies
have
not
explored
possibility
delivering
restore
adult
deaf
mice.
Here,
we
showed
that
aqueduct
mice
exhibits
lymphatic-like
characteristics.
In
vivo
time-lapse
magnetic
resonance
imaging,
computed
tomography,
optical
fluorescence
microscopy
large-particle
tracers
injected
into
reached
dispersive
transport
A
single
intracisternal
injection
adeno-associated
virus
carrying
solute
carrier
family
17,
member
8
(
Slc17A8
),
encodes
vesicular
glutamate
transporter-3
(VGLUT3),
rescued
−/−
restoring
VGLUT3
protein
expression
hair
cells,
minimal
ectopic
brain
none
liver.
Our
findings
demonstrate
comprises
an
accessible
route
represent
important
step
toward
using
Journal of Neuroscience,
Journal Year:
2023,
Volume and Issue:
43(27), P. 5057 - 5075
Published: June 2, 2023
Age-related
hearing
loss,
or
presbyacusis,
is
a
common
degenerative
disorder
affecting
communication
and
quality
of
life
for
millions
older
adults.
Multiple
pathophysiologic
manifestations,
along
with
many
cellular
molecular
alterations,
have
been
linked
to
presbyacusis;
however,
the
initial
events
causal
factors
not
clearly
established.
Comparisons
transcriptome
in
lateral
wall
(LW)
other
cochlear
regions
mouse
model
(of
both
sexes)
“normal”
age-related
loss
revealed
that
early
pathophysiological
alterations
stria
vascularis
(SV)
are
associated
increased
macrophage
activation
signature
indicative
inflammaging,
form
immune
dysfunction.
Structure-function
correlation
analyses
mice
across
lifespan
showed
age-dependent
increase
decline
auditory
sensitivity.
High-resolution
imaging
analysis
middle-aged
aged
human
cochleas,
transcriptomic
changes
gene
expression,
support
hypothesis
aberrant
activity
an
important
contributor
strial
dysfunction,
pathology,
loss.
Thus,
this
study
highlights
SV
as
primary
site
degeneration
dysregulation
system
indicators
pathology
Importantly,
novel
new
methods
described
here
now
provide
means
analyze
temporal
bones
way
had
previously
feasible
thereby
represent
significant
tool
otopathological
evaluation.
SIGNIFICANCE
STATEMENT
neurodegenerative
life.
Current
interventions
(primarily
aids
implants)
offer
imperfect
often
unsuccessful
therapeutic
outcomes.
Identification
crucial
development
treatments
diagnostic
tests.
Here,
we
find
SV,
nonsensory
component
cochlea,
structural
functional
humans
characterized
by
cell
activity.
We
also
establish
technique
evaluating
cochleas
from
bones,
but
understudied
area
research
because
lack
well-preserved
specimens
difficult
tissue
preparation
processing
approaches.
Ear and Hearing,
Journal Year:
2023,
Volume and Issue:
44(6), P. 1464 - 1484
Published: July 13, 2023
The
variability
in
outcomes
of
cochlear
implantation
is
largely
unexplained,
and
clinical
factors
are
not
sufficient
for
predicting
performance.
Genetic
have
been
suggested
to
impact
outcomes,
but
the
genetic
heterogeneity
hereditary
hearing
loss
makes
it
difficult
determine
interpret
postoperative
It
hypothesized
that
mutations
affect
neuronal
components
cochlea
auditory
pathway,
targeted
by
implant
(CI),
may
lead
poor
A
large
cohort
CI
recipients
was
studied
verify
this
hypothesis.This
study
included
a
German
(n
=
123
implanted
ears;
n
76
probands)
with
definitive
etiology
according
American
College
Medical
Genetics
(ACMG)/Association
Molecular
Pathology
(AMP)
guidelines
documented
audiological
outcomes.
All
patients
underwent
preoperative
examinations.
Postoperative
outcome
measures
were
based
on
at
least
1
year
follow-up
postlingual
onset
(>6
years)
5
years
children
congenital
or
pre/perilingual
(≤6
years).
analysis
performed
three
different
methods
single-gene
screening,
custom-designed
gene
panel
sequencing,
targeting
known
syndromic
nonsyndromic
genes,
whole-genome
sequencing.The
diagnosis
probands
involved
35
genes
61
clinically
relevant
(pathogenic,
likely
pathogenic)
variants.
With
regard
ears
123),
six
most
frequently
affected
affecting
nearly
one-half
GJB2
(21%;
26),
TMPRSS3
(7%;
9),
MYO15A
8),
SLC26A4
(5%;
6),
LOXHD1
USH2A
(each
4%;
5).
pathogenic
variants
influence
sensory
nonneural
structures
above
median
level
speech
performance
all
70%
[monosyllable
word
recognition
score
quiet
65
decibels
sound
pressure
(SPL)].
When
expression
categories
compared
demographic
(total
number
categories:
30),
expressed
spiral
ganglion
emerged
as
significant
factor
more
negatively
than
parameters.
An
ANOVA
reduced
set
10)
identified
five
detrimental
leading
poorer
highly
effects
(
p
<
0.001),
accounting
total
11.8%
observed
variance.
single
strongest
category
neural
3.1%
variance.The
relationship
between
molecular
diagnoses
revealed
variabilities.
Poor
cochlea,
supporting
"spiral
hypothesis."
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 19, 2024
Abstract
Tinnitus
is
a
heritable,
highly
prevalent
auditory
disorder
treated
by
multiple
medical
specialties.
Previous
GWAS
indicated
high
genetic
correlations
between
tinnitus
and
hearing
loss,
with
little
indication
of
differentiating
signals.
We
present
meta-analysis,
triple
previous
sample
sizes,
expand
to
non-European
ancestries.
in
596,905
Million
Veteran
Program
subjects
identified
39
loci,
genes
related
neuronal
synapses
cochlear
structural
support.
Applying
state-of-the-art
analytic
tools,
we
confirm
large
number
shared
variants,
but
also
distinct
architecture
tinnitus,
higher
polygenicity
proportion
variants
not
difficulty.
Tissue-expression
analysis
for
infers
broad
enrichment
across
most
brain
tissues,
contrast
Finally,
only
correlated
spectrum
psychiatric
disorders,
providing
potential
new
avenues
treatment.
This
study
establishes
as
separate
from
difficulties.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(10), P. 5391 - 5391
Published: May 15, 2024
Age-related
hearing
loss
(HL),
or
presbycusis,
is
a
complex
and
heterogeneous
condition,
affecting
significant
portion
of
older
adults
involving
various
interacting
mechanisms.
Metabolic
type
age-related
HL,
characterized
by
the
dysfunction
stria
vascularis,
which
crucial
for
maintaining
endocochlear
potential
necessary
hearing.
Although
attention
on
metabolic
presbycusis
has
waned
in
recent
years,
research
continues
to
identify
strial
pathology
as
key
factor
HL.
This
narrative
review
integrates
past
research,
bridging
findings
from
animal
models
human
studies,
examine
contributions
vascularis
It
provides
brief
overview
structure
function
then
examines
mechanisms
contributing
dysfunction,
including
altered
ion
transport,
changes
pigmentation,
inflammatory
responses,
vascular
atrophy.
Importantly,
this
outlines
contribution
highlighting
areas
future
research.
emphasizes
interdependence
sensorineural
HL
highlights
importance
understanding
underlying
The
comprehensive
mechanistic
investigation
all
factors
cochlear
remains
identifying
developing
personalized,
protective,
restorative
treatments.
