Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy
Communications Biology,
Journal Year:
2025,
Volume and Issue:
8(1)
Published: Jan. 9, 2025
Activation
of
anaplerosis
takes
away
glutamine
from
the
biosynthetic
pathways
to
energy-producing
TCA
cycle.
Especially,
induction
hyperoxia
driven
in
neurovascular
tissues
such
as
retina
during
early
stages
development
could
deplete
precursors
newly
proliferating
endothelial
cells
impeding
physiological
angiogenesis
and
leading
vasoobliteration.
Using
an
oxygen-induced
retinopathy
(OIR)
mouse
model,
we
investigated
metabolic
differences
between
OIR-resistant
BALB/cByJ
OIR
susceptible
C57BL/6J
strains
at
system
levels
understand
molecular
underpinnings
that
potentially
contribute
hyperoxia-induced
vascular
abnormalities
neural
retina.
Our
systems
level
vivo
RNA-seq,
proteomics,
lipidomic
profiling
ex-vivo
retinal
explant
studies
show
medium-chain
fatty
acids
serves
alternative
source
feed
findings
strongly
implicate
suppress
glutamine-fueled
ameliorate
conditions
prematurity.
Medium
chain
acid
metabolism
differs
resistant
strains.
Hyperoxia
induces
medium
utilization
preventing
hyperoxic
conditions.
Language: Английский
Differential expression profiling and functional prediction of circRNA in hypoxia-induced human retinal microvascular endothelial cells
Juan Chen,
No information about this author
Ning Wang,
No information about this author
Jing Li
No information about this author
et al.
Research Square (Research Square),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 28, 2025
Abstract
Background
Retinopathy
of
prematurity
(ROP)
is
a
severe
retinal
disorder
primarily
affecting
premature
infants,
characterized
by
abnormal
blood
vessel
development.
The
pathogenesis
ROP
closely
linked
to
hypoxic
conditions,
with
human
microvascular
endothelial
cells
(HRMECs)
being
particularly
sensitive
hypoxia.
Despite
advancements
in
understanding
ROP,
the
precise
molecular
mechanisms
underlying
its
development
remain
poorly
understood.
Recent
studies
have
identified
involvement
circular
RNAs
(circRNAs)
various
diseases,
including
disorders,
but
their
role
remains
unclear.
Methods
This
study
established
cell
model
using
HRMECs
and
analyzed
differential
expression
profiles
circRNAs
induced
hypoxia
whole-transcriptome
sequencing.
Differentially
expressed
(DE-circRNAs)
were
validated
through
qRT-PCR,
functional
analyses,
Gene
Ontology
(GO)
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
pathway
analysis,
conducted.
Bioinformatics
techniques
employed
construct
circRNA-miRNA-mRNA
regulatory
networks.
Results
A
total
1,714
differentially
between
normoxic
groups,
899
upregulated
815
downregulated
(fold-change
≥
2,
p
≤
0.05).
GO
analysis
revealed
that
DE-circRNAs
involved
cellular
processes,
while
KEGG
several
associated
pathways.
CircRNA-miRNA-mRNA
networks
indicated
may
contribute
circRNA-targeted
miRNA-mRNA
axis.
Conclusions
profile
HRMEC
model.
findings
suggest
hsa_circ_0140253/hsa-miR-210-3p/ERFR
hsa_circ_0140253/hsa-miR-210-3p/PPARGC1A
pathways
are
via
sponge
mechanism.
Language: Английский
Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy
Neural Regeneration Research,
Journal Year:
2024,
Volume and Issue:
20(2), P. 366 - 377
Published: April 3, 2024
Retinal
aging
has
been
recognized
as
a
significant
risk
factor
for
various
retinal
disorders,
including
diabetic
retinopathy,
age-related
macular
degeneration,
and
glaucoma,
following
growing
understanding
of
the
molecular
underpinnings
their
development.
This
comprehensive
review
explores
mechanisms
investigates
potential
neuroprotective
approaches,
focusing
on
activation
transcription
EB.
Recent
meta-analyses
have
demonstrated
promising
outcomes
EB-targeted
strategies,
such
exercise,
calorie
restriction,
rapamycin,
metformin,
in
patients
animal
models
these
common
diseases.
The
critically
assesses
role
EB
biology
during
aging,
its
effects,
therapeutic
disorders.
impact
is
cell-specific,
influencing
metabolic
reprogramming
energy
homeostasis
neurons
through
regulation
mitochondrial
quality
control
nutrient-sensing
pathways.
In
vascular
endothelial
cells,
controls
important
processes,
cell
proliferation,
tube
formation,
nitric
oxide
levels,
thereby
inner
blood-retinal
barrier,
angiogenesis,
microvasculature.
Additionally,
affects
smooth
muscle
inhibiting
calcification
atherogenesis.
pigment
epithelial
modulates
functions
autophagy,
lysosomal
dynamics,
clearance
lipofuscin,
promoting
photoreceptor
survival
regulating
growth
A
expression
involved
neovascularization.
These
cell-specific
significantly
encompassing
proteostasis,
neuronal
synapse
plasticity,
metabolism,
microvasculature,
inflammation,
ultimately
offering
protection
against
emphasizes
target
Therefore,
it
imperative
to
obtain
well-controlled
direct
experimental
evidence
confirm
efficacy
modulation
diseases
while
minimizing
adverse
effects.
Language: Английский
Exploring endocrine FGFs - structures, functions and biomedical applications
Phuc Phan,
No information about this author
Gaёtane Ternier,
No information about this author
Oshadi Edirisinghe
No information about this author
et al.
International Journal of Biochemistry and Molecular Biology,
Journal Year:
2024,
Volume and Issue:
15(4), P. 68 - 99
Published: Jan. 1, 2024
The
family
of
fibroblast
growth
factors
(FGFs)
consists
22
members
with
diverse
biological
functions
in
cells,
from
cellular
development
to
metabolism.
can
be
further
categorized
into
three
subgroups
based
on
their
modes
action.
FGF19,
FGF21,
and
FGF23
are
endocrine
FGFs
that
act
a
hormone-like/endocrine
manner
regulate
various
metabolic
activities.
However,
all
the
require
both
FGF
receptors
(FGFRs)
klotho
co-receptors
elicit
functions.
α-klotho
β-klotho
as
scaffolds
bring
closer
form
active
complexes.
Numerous
novel
studies
about
FGFs'
structures,
mechanisms,
physiological
insights
have
been
published
understand
complex
molecular
interactions
activities
FGFs.
Herein,
we
aim
review
functions,
binding
mechanisms
cognate
receptors,
biomedical
applications
recent
years.
Language: Английский
Bidirectional causality of physical exercise in retinal neuroprotection
Neural Regeneration Research,
Journal Year:
2024,
Volume and Issue:
20(12), P. 3400 - 3415
Published: Dec. 16, 2024
Physical
exercise
is
recognized
as
an
effective
intervention
to
improve
mood,
physical
performance,
and
general
well-being.
It
achieves
these
benefits
through
cellular
molecular
mechanisms
that
promote
the
release
of
neuroprotective
factors.
Interestingly,
reduced
levels
have
been
implicated
in
several
central
nervous
system
diseases,
including
ocular
disorders.
Emerging
evidence
has
suggested
are
significantly
lower
individuals
with
diseases
such
glaucoma,
age-related
macular
degeneration,
retinitis
pigmentosa,
diabetic
retinopathy.
may
a
effect
on
retina.
Therefore,
association
between
involve
bidirectional
causal
relationship
whereby
visual
impairment
leads
decreased
exacerbates
development
disease.
In
this
review,
we
summarize
linking
eye
disease
identify
potential
mediators
exercise-induced
retinal
neuroprotection.
Finally,
discuss
future
directions
for
preclinical
clinical
research
health.
Language: Английский
Postnatal hyperglycemia alters amino acid profile in retinas (model of Phase I ROP)
iScience,
Journal Year:
2023,
Volume and Issue:
26(10), P. 108021 - 108021
Published: Sept. 22, 2023
Nutritional
deprivation
occurring
in
most
preterm
infants
postnatally
can
induce
hyperglycemia,
a
significant
and
independent
risk
factor
for
suppressing
physiological
retinal
vascularization
(Phase
I
retinopathy
of
prematurity
(ROP)),
leading
to
compensatory
but
pathological
neovascularization.
Amino
acid
supplementation
reduces
neovascularization
mice.
Little
is
known
about
amino
contribution
Phase
ROP.
In
mice
modeling
hyperglycemia-associated
ROP,
we
found
changes
acids
(including
decreased
L-leucine,
L-isoleucine,
L-valine).
Parenteral
L-isoleucine
suppressed
vascularization.
premature
infants,
severe
ROP
was
associated
with
higher
mean
intake
parenteral
versus
enteral
the
first
two
weeks
life
after
adjustment
treatment
group,
gestational
age
at
birth,
birth
weight,
sex.
The
number
days
support
independently
predicted
Further
understanding
modulating
may
help
improve
nutritional
intervention
prevent
Language: Английский
Systems levels analysis of lipid metabolism in oxygen-induced retinopathy
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Nov. 22, 2023
Hyperoxia
induces
glutamine-fueled
anaplerosis
in
the
Muller
cells,
endothelial
and
retinal
explants.
Anaplerosis
takes
away
glutamine
from
biosynthetic
pathway
to
energy-producing
TCA
cycle.
This
process
depletes
precursors
newly
proliferating
cells.
The
induction
of
hyperoxic
retina
is
a
compensatory
response,
either
decreased
glycolysis
or
flux
We
hypothesized
that
by
providing
substrates
feed
into
TCA,
we
could
reverse
prevent
anaplerosis,
thereby
abating
wastage
for
energy
generation.
Using
an
oxygen-induced
retinopathy
(OIR)
mouse
model,
first
compared
difference
fatty
acid
metabolism
between
OIR-resistant
BALB/cByJ
OIR
susceptible
C57BL/6J
strains
understand
if
these
exhibit
metabolic
protects
conditions
prevents
their
vasculature
model.
Based
on
our
findings
comparison
two
strains,
medium-chain
acid,
octanoate,
can
serve
as
alternative
source
response
hyperoxia.
Our
systems
levels
analysis
model
shows
medium
chain
TCA.
here,
time,
demonstrate
use
octanoate
replenish
normoxic
at
higher
rate
conditions.
Language: Английский
Protective Effects of Butyrate on Retinal Neovascularization in Preclinical Retinopathy of Prematurity Models
Allston Oxenrider,
No information about this author
Tommy Bui,
No information about this author
John Lester
No information about this author
et al.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 4, 2024
Abstract
Retinopathy
of
prematurity
(ROP)
remains
a
leading
cause
childhood
blindness
worldwide,
necessitating
new
therapeutic
strategies.
Current
interventions
targeting
advanced
disease
stages
often
fail
to
prevent
long-term
visual
impairment.
This
study
investigates
the
potential
sodium
butyrate
(NaB),
an
orally
administered
short-chain
fatty
acid,
in
preclinical
models
ROP.
Using
oxygen-induced
retinopathy
(OIR)
mouse
model,
we
demonstrate
that
daily
oral
NaB
supplementation
significantly
protects
against
pathological
angiogenesis,
impacting
not
only
vascular
but
also
neuronal
and
microglial
pathology
inner
retina.
Notably,
shows
efficacy
early-phase
ROP
intervention,
as
evidenced
by
studies
post-natal
day
9
(P9)
OIR
mice
novel
hyperglycemia-associated
(HAR)
which
mimics
hyperglycemic
conditions
many
premature
infants.
These
findings
highlight
promising
alternative
or
adjunct
therapy
current
anti-VEGF
treatments,
offering
protection
across
multiple
retinal
cell
types
development.
The
underscores
need
for
further
research
elucidate
specific
mechanisms
NaB’s
action,
paving
way
its
clinical
application
management.
marks
first
exploration
preventative
agent
ROP,
setting
stage
additional
evaluations
optimization.
Highlights
Sodium
(NaB)
significant
angiogenesis
model.
impacts
highlights
intervention
(ROP).
is
investigate
Language: Английский
Progress in the study of association between hematological indicators and retinopathy of prematurity (Review)
Biomedical Reports,
Journal Year:
2024,
Volume and Issue:
21(2)
Published: June 6, 2024
Retinopathy
of
prematurity
(ROP)
is
a
retinopathy
caused
by
abnormal
proliferation
blood
vessels
in
premature
infants.
It
can
lead
to
retinal
detachment
and,
severe
cases,
blindness,
rendering
ROP
critical
condition.
Advances
neonatal
medicine
have
improved
survival
rates
low
birth
weight
and
gestational
age
However,
this
progress
has
also
led
rise
incidence
ROP.
Currently,
birth,
high
postpartum
oxygen
levels
are
independent
risk
factors
for
Other
include
mode
delivery,
multiple
births,
anemia,
transfusion,
maternal
pregnancy
factors,
bronchopulmonary
dysplasia,
use
surfactants,
arterial
ductus
arteriosus
necrotizing
enterocolitis.
Laboratory
indicators
infants
such
as
platelet
count,
glucose,
inflammatory
cells,
lipid
hemoglobin
transfusion
may
be
associated
with
the
etiology
pathogenesis
not
fully
understood.
A
number
influence
onset
progression
ROP,
including
decreased
counts,
levels,
increased
white
cell
glucose
disorders
metabolism.
The
present
study
reviewed
effects
hemoglobin,
cells
lipids,
plasma
metabolic
pathways
on
Language: Английский