Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis
MedComm,
Год журнала:
2024,
Номер
5(4)
Опубликована: Апрель 1, 2024
Abstract
Autoimmune
uveitis
(AU)
is
a
kind
of
immune‐mediated
disease
resulting
in
irreversible
ocular
damage
and
even
permanent
vision
loss.
However,
the
precise
mechanism
underlying
dynamic
immune
changes
contributing
to
initiation
progression
AU
remains
unclear.
Here,
we
induced
an
experimental
(EAU)
model
with
IRBP
651‐670
found
that
day[D]14
was
inflammatory
summit
remarking
clinical
histopathological
manifestations
activation
retinal
microglia
exhibited
time‐dependent
pattern
EAU
course.
We
conducted
single‐cell
RNA
sequencing
cells
mice
at
four
time
points
constituting
largest
proportion,
especially
on
D14.
A
novel
subtype
(
Cd74
high
Ccl5
)
identified
peak
closely
associated
modulating
responses.
In
vitro
experiments
indicated
stimuli
proinflammatory
upregulation
CD74
CCL5,
overexpression
elicited
their
phenotype
via
nuclear
factor‐kappa
B
signaling
could
be
attenuated
by
treatment
neutralizing
CCL5
antibody
certain
extent.
In‐vivo
blockade
effectively
alleviated
microglial
EAU.
Therefore,
propose
targeting
as
promising
strategies
for
treatment.
Язык: Английский
Ocular immune‐related diseases: molecular mechanisms and therapy
MedComm,
Год журнала:
2024,
Номер
5(12)
Опубликована: Ноя. 28, 2024
Abstract
Ocular
immune‐related
diseases,
represent
a
spectrum
of
conditions
driven
by
immune
system
dysregulation,
include
but
not
limit
to
uveitis,
diabetic
retinopathy,
age‐related
macular
degeneration,
Graves’
ophthalmopathy,
etc.
The
molecular
and
cellular
mechanisms
underlying
these
diseases
are
typically
dysfunctioned
responses
targeting
ocular
tissues,
resulting
in
inflammation
tissue
damage.
Recent
advances
have
further
elucidated
the
pivotal
role
different
development,
progression,
as
well
management
various
diseases.
However,
there
is
currently
relative
lack
connection
between
treatments
several
In
this
review,
we
discuss
recent
findings
related
immunopathogenesis
above‐mentioned
particular,
summarize
types
cells,
inflammatory
mediators,
associated
signaling
pathways
that
involved
pathophysiology
ophthalmopathies.
Furthermore,
also
future
directions
utilizing
anti‐inflammatory
regime
This
will
facilitate
better
understanding
pathogenesis
provide
new
insights
for
treatment
approaches.
Язык: Английский
Microglial-mediated immune mechanisms in autoimmune uveitis: Elucidating pathogenic pathways and targeted therapeutics
Journal of Neuroimmunology,
Год журнала:
2024,
Номер
395, С. 578433 - 578433
Опубликована: Авг. 14, 2024
Язык: Английский
Comparative models of uveitis
Eye,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 18, 2025
Abstract
Several
clinical
subtypes
of
uveitis
exist
yet
specific
immunopathogenic
mechanisms
involved
remain
unclear.
Ex
vivo
studies
are
limited
by
lack
fresh
retinal
biopsies
and
have
relied
on
aqueous
humour
or
peripheral
blood,
which
may
not
directly
reflect
disease.
The
aim
this
review
is
to
compare
the
various
in
models
their
contributions
our
understanding
disease
processes.
These
models,
although
unable
all
signs,
provided
insight
into
contribution
genes
molecules,
characterisation
effector
T-cells,
cell
trafficking
tissues,
tissue-resident
myeloid
cells
mechanism(s)
action
several
anti-inflammatory
compounds.
In
an
excellent
resource
with
study
molecular
cellular
processes
involved.
Recent
refinements
improved
imaging,
application
omics
greatly
increased
number
readouts
translational
opportunities.
Future
approaches
vitro
will
also
be
discussed.
Язык: Английский
Transcriptomic analysis unveils bona fide molecular signatures of microglia under conditions of homeostasis and viral encephalitis
Journal of Neuroinflammation,
Год журнала:
2024,
Номер
21(1)
Опубликована: Авг. 17, 2024
Microglia
serve
as
a
front-line
defense
against
neuroinvasive
viral
infection,
however,
determination
of
their
actual
transcriptional
profiles
under
conditions
health
and
disease
is
challenging.
Here,
we
used
various
experimental
approaches
to
delineate
the
landscape
microglia
during
infection.
Intriguingly,
multiple
activation
genes
were
found
be
artificially
induced
in
sorted
demonstrated
that
shear
stress
encountered
cell
sorting
was
one
key
inducers.
Post-hoc
analysis
revealed
publicly
available
large-scale
single-cell
RNA
sequencing
datasets
significantly
tainted
by
aberrant
signatures
are
associated
with
sorting.
By
exploiting
ribosomal
tagging
approach,
developed
strategy
enrich
microglia-specific
transcripts
comparing
immunoprecipitated
total
RNA.
Such
enriched
instrumental
defining
bona
fide
virus
These
unified
microglial
may
benchmark
retrospectively
assess
ex
vivo
artefacts
from
atlases.
Leveraging
translatome,
enrichment
implicated
T-cell
cytokine
production
course
VSV
data
linked
re-stimulation
further
underscored
involved
shaping
antiviral
responses
brain.
Collectively,
our
study
defines
steady
state
encephalitis
highlights
cellular
interactions
between
T
cells
contribute
control
dissemination.
Язык: Английский
Multi-omics in exploring the pathophysiology of diabetic retinopathy
Frontiers in Cell and Developmental Biology,
Год журнала:
2024,
Номер
12
Опубликована: Дек. 11, 2024
Diabetic
retinopathy
(DR)
is
a
leading
global
cause
of
vision
impairment,
with
its
prevalence
increasing
alongside
the
rising
rates
diabetes
mellitus
(DM).
Despite
retina's
complex
structure,
underlying
pathology
DR
remains
incompletely
understood.
Single-cell
RNA
sequencing
(scRNA-seq)
and
recent
advancements
in
multi-omics
analyses
have
revolutionized
molecular
profiling,
enabling
high-throughput
analysis
comprehensive
characterization
biological
systems.
This
review
highlights
significant
contributions
scRNA-seq,
conjunction
other
technologies,
to
research.
Integrated
scRNA-seq
transcriptomic
revealed
novel
insights
into
pathogenesis,
including
alternative
transcription
start
site
events,
fluctuations
cell
populations,
altered
gene
expression
profiles,
critical
signaling
pathways
within
retinal
cells.
Furthermore,
by
integrating
genetic
association
studies
analyses,
researchers
identified
biomarkers,
susceptibility
genes,
potential
therapeutic
targets
for
DR,
emphasizing
importance
specific
types
disease
progression.
The
integration
metabolomics
has
also
been
instrumental
identifying
metabolites
dysregulated
associated
DR.
It
highly
conceivable
that
continued
synergy
between
approaches
will
accelerate
discovery
mechanisms
development
interventions
Язык: Английский
Gene therapy: New and future treatments for uveitis
Eye & ENT Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 12, 2024
Abstract
Uveitis,
characterized
by
intraocular
inflammation,
has
significant
management
challenges
due
to
its
diverse
etiologies
and
complicated
pathophysiology.
The
current
first‐line
treatments
primarily
aim
calm
inflammation
with
the
underlying
causes
unaffected,
often
associated
systemic
side
effects,
limited
long‐term
efficacy,
disease
recurrence.
Gene
therapies,
as
powerful
therapeutic
approaches,
have
been
applied
treat
various
genetic
non‐genetic
diseases.
However,
development
of
gene
therapy
for
uveitis
investigated
less.
This
review
discusses
possible
targets
approaches
analyzing
some
research
examples
in
exogenous
expression,
RNAi,
antisense
therapy,
CRISPR
editing
system.
Furthermore,
we
discuss
limitations
listed
therapies
propose
future
directions
potential
strategies
overcome
challenges.
Язык: Английский