Pharmacology Research & Perspectives,
Год журнала:
2024,
Номер
13(1)
Опубликована: Дек. 26, 2024
ABSTRACT
The
lack
of
effective
treatments
for
dry
age‐related
macular
degeneration
(AMD)
is
in
part
due
to
a
preclinical
animal
model
that
recapitulates
features
the
clinical
state
including
retinal
pigment
epithelium
(RPE)
degeneration,
also
known
as
geographic
atrophy
(GA).
A
nonhuman
primate
GA
was
developed
and
its
responsiveness
an
approved
treatment,
avacincaptad
pegol
(ACP),
complement
C5
inhibitor,
evaluated.
Intravitreal
(ivt)
administration
sodium
iodate
(SI)
into
one
eye
male
Macaca
fascicularis
leads
areas
(mm
2
)
hyper‐
or
hypo‐autofluorescence.
Qualitative
changes
structure
over
time
were
observed
with
spectral
domain
optical
coherence
tomography
(OCT).
Six
days
after
SI
administration,
prior
mean
(±
SEM)
all
eyes
8.2
±
1.8
mm
.
Following
randomization
treatment
groups,
either
vehicle
ACP
ivt
injected
continued
every
4
weeks,
total
four
treatments.
Sixteen
weeks
area
vehicle‐treated
18.9
6.6
,
whereas
ACP‐treated
11.4
4.0
reduction
by
about
36%.
Increased,
followed
decreased,
overall
thickness
OCT
following
administration.
Treatment
did
not
change
alter
thinning.
Geographic
atrophy‐like
lesions
expand
are
current
macaque
could
be
utilized
further
explore
mechanism
AMD
develop
more
novel
therapeutics.
Cells,
Год журнала:
2025,
Номер
14(5), С. 324 - 324
Опубликована: Фев. 20, 2025
Heart
failure
(HF)
is
a
prominent
fatal
cardiovascular
disorder
afflicting
3.4%
of
the
adult
population
despite
advancement
treatment
options.
Therefore,
better
understanding
pathogenesis
HF
essential
for
exploring
novel
therapeutic
strategies.
Hypertrophy
and
fibrosis
are
significant
characteristics
pathological
cardiac
remodeling,
contributing
to
HF.
The
mechanisms
involved
in
development
remodeling
consequent
multifactorial,
this
review,
key
underlying
discussed.
These
have
been
divided
into
following
categories
thusly:
(i)
mitochondrial
dysfunction,
including
defective
dynamics,
energy
production,
oxidative
stress;
(ii)
lipotoxicity;
(iii)
maladaptive
endoplasmic
reticulum
(ER)
(iv)
impaired
autophagy;
(v)
inflammatory
responses;
(vi)
programmed
cell
death,
apoptosis,
pyroptosis,
ferroptosis;
(vii)
endothelial
dysfunction;
(viii)
contractility.
Preclinical
data
suggest
that
there
merit
targeting
identified
pathways;
however,
their
clinical
implications
outcomes
regarding
treating
need
further
investigation
future.
Herein,
we
introduce
molecular
pivotal
onset
progression
HF,
as
well
compounds
related
potential
preventing
or
rescuing
This,
therefore,
offers
an
avenue
design
discovery
therapies
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(5), С. 2334 - 2334
Опубликована: Март 5, 2025
Oxidative
stress-induced
photoreceptor
cell
death
is
closely
associated
with
the
etiology
of
age-related
macular
degeneration
(AMD),
and
sodium
iodate
(SI)
has
been
widely
used
as
an
oxidant
stimulus
in
AMD
models
to
induce
retinal
pigment
epithelium
(RPE)
death.
However,
mechanism
underlying
SI-induced
remains
controversial
unclear.
In
this
study,
we
elucidate
that
ferroptosis
a
critical
form
induced
by
SI
photoreceptor-derived
661W
cells.
disrupts
system
Xc-,
leading
glutathione
(GSH)
depletion
triggering
lipid
peroxidation,
thereby
promoting
Additionally,
enhances
intracellular
Fe2+
levels,
which
further
facilitates
reactive
oxygen
species
(ROS)
accumulation,
making
cells
more
susceptible
ferroptosis.
Exogenous
GSH,
well
specific
inhibitors
such
Fer-1
antioxidants
like
NAC,
significantly
attenuate
These
findings
provide
new
insights
into
mechanisms
key
pathway
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1413 - 1413
Опубликована: Фев. 7, 2025
Age-related
macular
degeneration
(AMD)
is
a
leading
cause
of
vision
impairment
in
people
over
the
age
60.
Currently,
FDA-approved
drugs
for
AMD
have
various
side
effects,
and
there
notable
lack
drug
development
dry
AMD.
This
study
aimed
to
explore
therapeutic
effects
mono-ethyl
fumarate
(MEF)
on
MEF
effectively
protected
ARPE-19
cells
from
cell
death
induced
by
combination
A2E
blue
light
exposure.
In
C57BL/6J
mouse
model
retinal
caused
sodium
iodate,
played
role
preserving
thickness
maintaining
layered
structure
retina.
It
was
assessed
via
fundus
imaging,
optical
coherence
tomography,
hematoxylin
eosin
staining.
Treatment
with
significantly
increased
expression
antioxidant
proteins
such
as
HO-1,
NQO1,
SOD1
cells.
Additionally,
treatment
levels
GPX4
Concurrently,
it
reduced
apoptosis-related
factors,
Bax/Bcl-2
ratio
Caspase
-3
cleavage.
These
findings
suggest
that
may
represent
promising
candidate
management
Antioxidants,
Год журнала:
2023,
Номер
12(12), С. 2129 - 2129
Опубликована: Дек. 17, 2023
Chronic
oxidative
stress
impairs
the
normal
functioning
of
retinal
pigment
epithelium
(RPE),
leading
to
atrophy
this
cell
layer
in
cases
advance
age-related
macular
degeneration
(AMD).
The
purpose
our
study
was
determine
if
buspirone,
a
partial
serotonin
1A
(5-HT1A)
receptor
agonist,
protected
against
stress-induced
changes
RPE.
We
exposed
differentiated
human
ARPE-19
cells
paraquat
induce
damage
culture,
and
utilized
mouse
model
with
sodium
iodate
(NaIO3)-induced
injury
evaluate
effect
buspirone.
To
investigate
buspirone’s
on
protective
gene
expression,
we
performed
RT–PCR.
Cellular
toxicities
junctional
abnormalities
due
induction
impact
were
assessed
via
WST-1
assays
ZO-1
immunostaining.
used
spectral-domain
optical
coherence
tomography
(SD-OCT)
immunostaining
RPE/choroid
for
structural
analysis.
showed
dose-dependent
protection
viability
buspirone-treated
culture
preservation
RPE
integrity
under
conditions.
In
NaIO3
model,
daily
intraperitoneal
injection
(i.p.)
buspirone
(30
mg/kg)
12
days
improved
survival
photoreceptors
compared
those
vehicle-treated
eyes.
ZO-1-stained
flat-mounts
revealed
from
mice,
as
well
buspirone-induced
Nqo1,
Cat,
Sqstm1,
Gstm1,
Sod2
genes
untreated
Since
is
implicated
pathogenesis
AMD,
repurposing
which
currently
approved
treatment
anxiety,
might
be
useful
treating
or
preventing
dry
AMD.
Advanced Healthcare Materials,
Год журнала:
2024,
Номер
13(30)
Опубликована: Авг. 11, 2024
Ferrous
ion
accumulation
and
lethal
oxidative
stress
mediate
irreversible
retinal
pigment
epithelial
(RPE)
cell
ferroptosis
subsequent
photoreceptor
degeneration,
a
potential
key
pathogenic
factor
in
the
onset
of
dry
age-related
macular
degeneration
(dAMD),
causing
vision
loss
global
elderly
population.
However,
currently,
no
effective
interventional
treatment
strategy
exists
clinical
practice.
Herein,
lesion
site-targeted
melanin-like
nanoparticles,
named
ConA-MelNPs,
are
designed
as
novel
inhibitor
for
degenerative
diseases.
ConA-MelNPs
possessed
chelating
iron
characteristics,
alleviating
severe
mitochondrial
damage
caused
by
protecting
RPE
cells
from
induced
sodium
iodate
(NaIO
