bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 25, 2024
ABSTRACT
Neurons
use
cell-adhesion
molecules
(CAMs)
to
interact
with
other
neurons
and
the
extracellular
environment:
combination
of
CAMs
specifies
migration
patterns,
neuronal
morphologies,
synaptic
connections
across
diverse
neuron
types.
Yet
little
is
known
regarding
intracellular
signaling
cascade
mediating
CAM
recognitions
at
cell
surface
different
In
this
study,
we
investigated
neural
developmental
role
Afadin
1–4
,
a
cytosolic
adapter
protein
that
connects
multiple
families
F-actin.
We
introduced
conditional
mutant
5
an
embryonic
retinal
Cre,
Six3-Cre
6–8
.
reported
mutants
lead
scrambled
distribution,
including
Bipolar
Cells
(BCs),
Amacrine
(ACs),
ganglion
cells
(RGCs),
three
cellular
layers
retina.
This
pattern
was
first
here
neuron-type
resolution.
Importantly,
do
not
display
deficits
for
BCs,
ACs,
or
RGCs
in
terms
fate
specifications
survival.
Additionally,
displayed
RGC
types
still
maintain
partners
putative
AC
types,
indicating
molecular
determinants
instruct
choices
independent
Afadin.
Lastly,
there
significant
decline
visual
function
mis-targeting
axons
incorrect
zones
superior
colliculus,
one
major
retinorecipient
areas.
Collectively,
our
study
uncovers
unique
sorting
into
proper
as
structural
basis
orderly
processing.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Март 11, 2024
Previous
studies
of
neuronal
survival
have
primarily
focused
on
identifying
intrinsic
mechanisms
controlling
the
process.
This
study
explored
how
intercellular
communication
contributes
to
retinal
ganglion
cell
(RGC)
following
optic
nerve
crush
based
single-cell
RNA-seq
analysis.
We
observed
transcriptomic
changes
in
cells
response
injury,
with
astrocytes
and
Müller
glia
having
most
interactions
RGCs.
By
comparing
RGC
subclasses
characterized
by
distinct
resilience
death,
we
found
that
high-survival
RGCs
tend
more
ligand-receptor
neighboring
cells.
identified
47
stronger
RGCs,
likely
mediating
neuroprotective
effects.
validated
one
target,
μ-opioid
receptor
(Oprm1),
be
three
injury
models.
Although
endogenous
Oprm1
is
preferentially
expressed
intrinsically
photosensitive
its
effect
can
transferred
other
pan-RGC
overexpression
Oprm1.
Lastly,
manipulating
activity
improved
visual
functions
mice.
Journal of Neuroscience,
Год журнала:
2023,
Номер
44(5), С. e1310232023 - e1310232023
Опубликована: Дек. 14, 2023
Maintaining
precise
synaptic
contacts
between
neuronal
partners
is
critical
to
ensure
the
proper
functioning
of
mammalian
central
nervous
system
(CNS).
Diverse
cell
recognition
molecules,
such
as
classic
cadherins
(Cdhs),
are
part
molecular
machinery
mediating
choices
during
development
and
maintenance.
Yet,
principles
governing
neuron–neuron
wiring
across
diverse
CNS
neuron
types
remain
largely
unknown.
The
retinotectal
synapses,
connections
from
retinal
ganglion
cells
(RGCs)
superior
collicular
(SC)
neurons,
offer
an
ideal
experimental
reveal
logic
underlying
formation.
This
due
retina's
unidirectional
laminar-restricted
projections
SC
large
databases
presynaptic
RGC
subtypes
postsynaptic
types.
Here,
we
focused
on
determining
role
Type
II
Cdhs
in
synapses.
We
surveyed
expression
patterns
at
resolution
revealed
that
Cdh13
enriched
wide-field
neurons
superficial
(sSC).
In
either
null
mutant
or
selective
adult
deletion
within
there
a
significant
reduction
spine
densities
distal
dendrites
these
both
sexes.
Additionally,
removal
RGCs
reduced
dendritic
spines
neurons.
Cdh13-expressing
use
differential
mechanisms
than
αRGCs
On–Off
Direction-Selective
Ganglion
Cells
(ooDSGCs)
form
specific
results
transneuronal
interaction
mediated
by
maintain
synapses
vivo.
Frontiers in Neuroanatomy,
Год журнала:
2024,
Номер
18
Опубликована: Фев. 13, 2024
Purpose
The
aim
of
this
study
was
to
investigate,
the
neuroprotective
effects
a
new
Gramine
derivative
named:
ITH12657,
in
model
retinal
excitotoxicity
induced
by
intravitreal
injection
NMDA.
Methods
Adult
Sprague
Dawley
rats
received
an
100
mM
NMDA
their
left
eye
and
were
treated
daily
with
subcutaneous
injections
ITH12657
or
vehicle.
best
dose–response,
therapeutic
window
study,
optimal
treatment
duration
studied.
Based
on
survival
Brn3a
+
RGCs
obtained
from
above-mentioned
studies,
protective
studied
vivo
(retinal
thickness
full-field
Electroretinography),
ex
quantifying
surviving
population
RGCs,
αRGCs
subtypes
α-ONsRGCs,
α-ONtRGCs,
α-OFFRGCs.
Results
Administration
10
mg/kg
starting
12
h
before
dispensed
for
3
days,
resulted
significant
protection
against
NMDA-induced
excitotoxicity.
In
,
ITH12657-treated
showed
preservation
functional
Ex
results
that
afforded
populations
RGC,
αRGC,
αONs-RGC,
but
not
αOFF-RGC,
while
α-ONtRGC
fully
resistant
Conclusion
Subcutaneous
administration
at
mg/kg,
initiated
injury
continued
αONs-RGC
excitotoxicity-induced
RGC
death.
αOFF-RGCs
extremely
sensitive
α-ONtRGCs
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(13), С. 6995 - 6995
Опубликована: Июнь 26, 2024
Cataracts
and
glaucoma
account
for
a
high
percentage
of
vision
loss
blindness
worldwide.
Small
extracellular
vesicles
(sEVs)
are
released
into
different
body
fluids,
including
the
eye's
aqueous
humor.
Information
about
their
proteome
content
characterization
in
ocular
pathologies
is
not
yet
well
established.
In
this
study,
humor
sEVs
from
healthy
individuals,
cataracts,
patients
were
studied,
specific
protein
profiles
characterized.
Moreover,
potential
identified
proteins
as
diagnostic
biomarkers
was
evaluated.
The
patients'
with
cataracts
compared
to
individuals
analyzed
by
quantitative
proteomics.
Validation
performed
western
blot
(WB)
ELISA.
A
total
828
peptides
192
quantified.
After
data
analysis
R
program,
8
significantly
dysregulated
16
showed
an
expression
ratio
≥
1.5.
By
WB
ELISA
using
directly
samples,
dysregulation
9
mostly
confirmed.
Importantly,
GAS6
SPP1
ability
glaucoma,
which
combination
allowed
discriminating
control
area
under
curve
76.1%
sensitivity
65.6%
specificity
87.7%.
Investigative Ophthalmology & Visual Science,
Год журнала:
2025,
Номер
66(2), С. 14 - 14
Опубликована: Фев. 5, 2025
Purpose:
Melanopsin-expressing
intrinsically
photosensitive
(ip)
retinal
ganglion
cells
(RGCs)
can
be
divided
into
six
different
subtypes
(M1
–
M6).
Yet,
specific
markers
exist
for
only
some
of
these
that
could
employed
to
study
the
function
individual
subtypes.
Osteopontin
(Spp1)
marks
αRGC,
suggesting
that,
across
ipRGCs,
it
would
mark
M4-ipRGC
subtype
(synonymous
ON-sustained
αRGCs).
Recent
evidence
suggests
osteopontin
expression
spread
other
ipRGC
Therefore,
this
aims
characterize
pattern
in
mice.
Methods:
Single-cell
RNA
(scRNA-seq)
sequencing
data
from
murine
RGCs
were
analyzed
identify
patterns
Spp1
ipRGCs.
Immunohistochemistry
(IHC)
was
performed
on
cryosections
and
flatmounts
C57BL/6J
mice
localization
Neurite
tracing
dendritic
morphology
Results:
scRNA-seq
analysis
revealed
two
distinct
clusters
IHC
confirmed
colocalization
with
neurofilament
heavy
chain,
an
established
marker
αRGCs,
including
M4-ipRGCs.
immunoreactivity
moreover
identified
one
additional
group
By
stratification,
those
clearly
as
M2-ipRGCs.
Conclusions:
Our
findings
demonstrate
is
expressed
both
M2-
M4-ipRGCs,
challenging
notion
a
exclusively
αRGCs.
double-labeling
melanopsin
provides
novel
method
differentiate
M2
ipRGCs
This
will
support
physiology
-specific
manner
may,
instance,
foster
research
field
optic
nerve
injury.
Neurons
use
cell-adhesion
molecules
(CAMs)
to
interact
with
other
neurons
and
the
extracellular
environment:
combination
of
CAMs
specifies
migration
patterns,
neuronal
morphologies,
synaptic
connections
across
diverse
neuron
types.
Yet
little
is
known
regarding
intracellular
signaling
cascade
mediating
CAM
recognitions
at
cell
surface
different
In
this
study,
we
investigated
neural
developmental
role
Afadin
1–4
,
a
cytosolic
adapter
protein
that
connects
multiple
families
F-actin.
We
introduced
conditional
mutant
5
an
embryonic
retinal
Cre,
Six3-Cre
6–8
.
reported
mutants
lead
scrambled
distribution,
including
Bipolar
Cells
(BCs),
Amacrine
(ACs),
ganglion
cells
(RGCs),
three
cellular
layers
retina.
This
pattern
was
first
here
neuron-type
resolution.
Importantly,
do
not
display
deficits
for
BCs,
ACs,
or
RGCs
in
terms
fate
specifications
survival.
Additionally,
displayed
RGC
types
still
maintain
partners
putative
AC
types,
indicating
molecular
determinants
instruct
choices
independent
Afadin.
Lastly,
there
significant
decline
visual
function
mis-targeting
axons
incorrect
zones
superior
colliculus,
one
major
retinorecipient
areas.
Collectively,
our
study
uncovers
unique
sorting
into
proper
as
structural
basis
orderly
processing.
Neurons
use
cell-adhesion
molecules
(CAMs)
to
interact
with
other
neurons
and
the
extracellular
environment:
combination
of
CAMs
specifies
migration
patterns,
neuronal
morphologies,
synaptic
connections
across
diverse
neuron
types.
Yet
little
is
known
regarding
intracellular
signaling
cascade
mediating
CAM
recognitions
at
cell
surface
different
In
this
study,
we
investigated
neural
developmental
role
Afadin
1–4
,
a
cytosolic
adapter
protein
that
connects
multiple
families
F-actin.
We
introduced
conditional
mutant
5
an
embryonic
retinal
Cre,
Six3-Cre
6–8
.
reported
mutants
lead
scrambled
distribution,
including
Bipolar
Cells
(BCs),
Amacrine
(ACs),
ganglion
cells
(RGCs),
three
cellular
layers
retina.
This
pattern
was
first
here
neuron-type
resolution.
Importantly,
do
not
display
deficits
for
BCs,
ACs,
or
RGCs
in
terms
fate
specifications
survival.
Additionally,
displayed
RGC
types
still
maintain
partners
putative
AC
types,
indicating
molecular
determinants
instruct
choices
independent
Afadin.
Lastly,
there
significant
decline
visual
function
mis-targeting
axons
incorrect
zones
superior
colliculus,
one
major
retinorecipient
areas.
Collectively,
our
study
uncovers
unique
sorting
into
proper
as
structural
basis
orderly
processing.
The Journal of Physiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 22, 2025
Abstract
Retinal
ganglion
cells
(RGCs)
are
the
sole
output
neurons
of
retina
and
convey
visual
information
to
brain
via
their
axons
in
optic
nerve.
Following
injury
nerve,
RGC
degenerate
many
die.
For
example,
a
model
axon
injury,
nerve
crush
(ONC),
kills
∼80%
RGCs
after
2
weeks.
Surviving
biased
towards
‘resilient’
types,
including
several
with
sustained
firing
light
stimulation.
survival
may
depend
on
activity,
there
is
limited
understanding
how
or
why
activity
changes
following
injury.
Here
we
quantified
electrophysiological
properties
highly
resilient
type,
ON‐Alpha
(AlphaONS)
RGC,
7
days
ONC
extracellular
whole‐cell
patch
clamp
recording.
Both
light‐
current‐driven
were
reduced
ONC,
but
synaptic
inputs
largely
intact.
Resting
membrane
potential
input
resistance
relatively
unchanged,
while
voltage‐gated
currents
impaired,
reduction
sodium
channel
current
density
initial
segment.
Hyperpolarization
chelation
intracellular
calcium
partially
rescued
rates.
Extracellular
recordings
at
3
showed
normal
light‐evoked
from
AlphaONS
other
Alpha
RGCs,
susceptible
types.
These
data
suggest
that
an
injured
reduces
its
by
1
week
as
consequence
downregulation
intrinsic
excitability
Ca
2+
‐dependent
mechanism.
Reduced
be
due
degradation
could
also
energetically
beneficial,
preserving
energy
for
regeneration.
image
Key
points
cell
(RGC)
types
show
diverse
rates
A
type
(sustained
RGC)
maintains
The
shows
diminished
expression
segment
genes
Activity
deficits
reflect
dysfunction
(Na
+
channels,
),
not
input.
intact
suggesting
this
time
point
does
predict
resilience.
