PLoS ONE,
Год журнала:
2024,
Номер
19(8), С. e0308671 - e0308671
Опубликована: Авг. 8, 2024
Glaucoma
is
a
multifactorial
optic
neuropathy
that
primarily
affecting
retinal
ganglion
cells
(RGC).
Brimonidine
an
intraocular
pressure-lowering
drug
with
reported
neuroprotective
properties.
This
study
aimed
to
compare
the
effects
of
topical
and
intraperitoneal
(IP)
brimonidine
on
RGCs
from
different
segments
in
murine
nerve
crush
(ONC)
model.
Molecular Neurodegeneration,
Год журнала:
2022,
Номер
17(1)
Опубликована: Март 21, 2022
Across
neurodegenerative
diseases,
common
mechanisms
may
reveal
novel
therapeutic
targets
based
on
neuronal
protection,
repair,
or
regeneration,
independent
of
etiology
site
disease
pathology.
To
address
these
and
discuss
emerging
treatments,
in
April,
2021,
Glaucoma
Research
Foundation,
BrightFocus
the
Melza
M.
Frank
Theodore
Barr
Foundation
collaborated
to
bring
together
key
opinion
leaders
experts
field
for
a
virtual
meeting
titled
"Solving
Neurodegeneration".
This
"think-tank"
style
focused
uncovering
mechanistic
roots
promising
new
catalyzed
by
goal
finding
treatments
glaucoma,
world's
leading
cause
irreversible
blindness
interest
three
hosting
foundations.
Glaucoma,
which
causes
vision
loss
through
degeneration
optic
nerve,
likely
shares
early
cellular
molecular
events
with
other
diseases
central
nervous
system.
Here
we
major
areas
overlap
between
system:
neuroinflammation,
bioenergetics
metabolism,
genetic
contributions,
neurovascular
interactions.
We
summarize
important
discussion
points
emphasis
research
that
are
most
innovative
treatment
neurodegeneration
yet
require
further
development.
The
is
highlighted
provides
unique
opportunities
collaboration
will
lead
efforts
preventing
ultimately
loss.
Molecular Neurodegeneration,
Год журнала:
2024,
Номер
19(1)
Опубликована: Янв. 25, 2024
Abstract
The
extracellular
matrix
is
a
richly
bioactive
composition
of
substrates
that
provides
biophysical
stability,
facilitates
intercellular
signaling,
and
both
reflects
governs
the
physiological
status
local
microenvironment.
in
central
nervous
system
(CNS)
far
from
simply
an
inert
scaffold
for
mechanical
support,
instead
conducting
active
role
homeostasis
providing
broad
capacity
adaptation
remodeling
response
to
stress
otherwise
would
challenge
equilibrium
between
neuronal,
glial,
vascular
elements.
A
major
constituent
collagen,
whose
characteristic
triple
helical
structure
renders
biochemical
stability
enable
bidirectional
crosstalk
resident
cells.
Multiple
members
collagen
superfamily
are
critical
neuronal
maturation
circuit
formation,
axon
guidance,
synaptogenesis
brain.
In
mature
tissue,
interacts
with
other
fibrous
proteins
glycoproteins
sustain
three-dimensional
medium
through
which
complex
networks
cells
can
communicate.
While
scaffolding,
CNS
also
highly
dynamic,
multiple
binding
sites
partnering
proteins,
cell-surface
receptors,
ligands.
These
interactions
emerging
as
mediators
disease
injury,
particularly
regarding
changes
stiffness,
astrocyte
recruitment
reactivity,
pro-inflammatory
signaling
microenvironments.
Changes
and/or
deposition
impact
cellular
tissue
biomechanics
brain,
turn
alter
responses
including
antigenicity,
angiogenesis,
gliosis,
immune-related
factors,
each
involving
contribute
limited
regeneration
tissue.
Emerging
therapeutics
attempt
rebuild
using
peptide
fragments,
collagen-enriched
scaffolds
mimetics,
hold
great
potential
promote
neural
repair
regeneration.
Recent
evidence
our
group
others
indicates
repairing
protease-degraded
helices
mimetic
peptides
helps
restore
survival
spectrum
degenerative
conditions.
Restoration
likely
involves
bolstering
stiffness
reduce
reactivity
inflammation
well
inhibitory
immune-signaling
Facilitating
rather
than
endogenous
replacement
degraded
by
or
injury
may
represent
next
frontier
developing
therapies
based
on
protection,
repair,
neurons
system.
Aging and Disease,
Год журнала:
2024,
Номер
15(2), С. 546 - 546
Опубликована: Янв. 1, 2024
Aging
is
one
of
the
most
serious
risk
factors
for
glaucoma,
and
according
to
age-standardized
prevalence,
glaucoma
second
leading
cause
legal
blindness
worldwide.
Cellular
senescence
a
hallmark
aging
that
defined
by
stable
exit
from
cell
cycle
in
response
cellular
damage
stress.
The
potential
mechanisms
underlying
glaucomatous
include
oxidative
stress,
DNA
damage,
mitochondrial
dysfunction,
defective
autophagy/mitophagy,
epigenetic
modifications.
These
phenotypes
interact
generate
sufficiently
network
maintain
senescent
state.
Senescent
trabecular
meshwork
(TM)
cells,
retinal
ganglion
cells
(RGCs)
vascular
endothelial
reportedly
accumulate
with
age
stress
may
contribute
pathologies.
Therapies
targeting
suppression
or
elimination
have
been
found
ameliorate
RGC
death
improve
vision
models,
suggesting
pivotal
role
pathophysiology
glaucoma.
In
this
review,
we
explore
biological
links
between
specifically
delving
into
senescence.
Moreover,
summarize
current
data
on
key
target
associated
development
clinical
Finally,
discuss
therapeutic
management
Molecular Therapy,
Год журнала:
2022,
Номер
30(4), С. 1421 - 1431
Опубликована: Янв. 31, 2022
The
lack
of
neuroprotective
treatments
for
retinal
ganglion
cells
(RGCs)
and
optic
nerve
(ON)
is
a
central
challenge
glaucoma
management.
Emerging
evidence
suggests
that
redox
factor
NAD+
decline
hallmark
aging
neurodegenerative
diseases.
Supplementation
with
precursors
overexpression
NMNAT1,
the
key
enzyme
in
biosynthetic
process,
have
significant
effects.
We
first
profile
translatomes
RGCs
naive
mice
silicone
oil-induced
ocular
hypertension
(SOHU)/glaucoma
by
RiboTag
mRNA
sequencing.
Intriguingly,
only
NMNAT2,
but
not
NMNAT1
or
NMNAT3,
significantly
decreased
SOHU
glaucomatous
RGCs,
which
we
confirm
situ
hybridization.
next
demonstrate
AAV2
intravitreal
injection-mediated
long
half-life
NMNAT2
mutant
driven
RGC-specific
mouse
γ-synuclein
(mSncg)
promoter
restores
levels
ONs.
Moreover,
this
gene
therapy
strategy
delivers
neuroprotection
both
RGC
soma
axon
preservation
visual
function
traumatic
ON
crush
model
model.
Collectively,
our
studies
suggest
weakening
expression
contributes
to
deleterious
decline,
modulating
RGC-intrinsic
AAV2-mSncg
vector
promising
neurodegeneration.
Progress in Retinal and Eye Research,
Год журнала:
2024,
Номер
100, С. 101261 - 101261
Опубликована: Март 26, 2024
Glaucoma
is
the
leading
cause
of
irreversible
blindness
globally.
The
disease
causes
vision
loss
due
to
neurodegeneration
retinal
ganglion
cell
(RGC)
projection
brain
through
optic
nerve.
associated
with
sensitivity
intraocular
pressure
(IOP).
Thus,
mainstay
treatments
seek
manage
IOP,
though
many
patients
continue
lose
vision.
To
address
directly,
numerous
preclinical
studies
develop
protective
or
reparative
therapies
that
act
independently
IOP.
These
include
growth
factors,
compounds
targeting
metabolism,
anti-inflammatory
and
antioxidant
agents,
neuromodulators.
Despite
success
in
experimental
models,
these
approaches
fail
translate
into
clinical
benefits.
Several
factors
contribute
this
challenge.
Firstly,
anatomic
structure
nerve
head
differs
between
rodents,
nonhuman
primates,
humans.
Additionally,
animal
models
do
not
replicate
complex
glaucoma
pathophysiology
Therefore,
enhance
translating
findings,
we
propose
two
approaches.
First,
thorough
evaluation
targets
multiple
including
should
precede
trials.
Second,
advocate
for
combination
therapy,
which
involves
using
agents
simultaneously,
especially
early
potentially
reversible
stages
disease.
strategies
aim
increase
chances
successful
neuroprotective
treatment
glaucoma.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(15), С. 7994 - 7994
Опубликована: Июль 27, 2021
Retinal
ganglion
cells
(RGCs)
are
a
population
of
neurons
the
central
nervous
system
(CNS)
extending
with
their
soma
to
inner
retina
and
axons
optic
nerve.
Glaucoma
represents
group
neurodegenerative
diseases
where
slow
progressive
death
RGCs
results
in
permanent
loss
vision.
To
date,
although
Intra
Ocular
Pressure
(IOP)
is
considered
main
therapeutic
target,
precise
mechanisms
by
which
die
glaucoma
have
not
yet
been
clarified.
In
fact,
Primary
Open
Angle
(POAG),
most
common
form,
also
occurs
without
elevated
IOP.
This
present
review
provides
summary
some
pathological
conditions,
i.e.,
axonal
transport
blockade,
glutamate
excitotoxicity
changes
pro-inflammatory
cytokines
along
RGC
projection,
all
involved
cascade.
Moreover,
neuro-protective
approaches,
aim
improve
degeneration,
taken
into
consideration.
Frontiers in Neuroscience,
Год журнала:
2021,
Номер
15
Опубликована: Май 28, 2021
Glaucoma,
a
neurodegenerative
disease
that
leads
to
irreversible
vision
loss,
is
characterized
by
progressive
loss
of
retinal
ganglion
cells
(RGCs)
and
optic
axons.
To
date,
elevated
intraocular
pressure
(IOP)
has
been
recognized
as
the
main
phenotypic
factor
associated
with
glaucoma.
However,
some
patients
normal
IOP
also
have
glaucomatous
visual
impairment
RGC
loss.
Unfortunately,
underlying
mechanisms
behind
such
cases
remain
unclear.
Recent
studies
suggested
glia
play
significant
roles
in
initiation
progression
Multiple
types
glial
are
activated
Microglia,
for
example,
act
critical
mediators
orchestrate
neuroinflammation
through
pro-inflammatory
cytokines.
In
contrast,
macroglia
(astrocytes
Müller
cells)
participate
inflammatory
responses
modulators
contribute
neuroprotection
secretion
neurotrophic
factors.
Notably,
research
results
indicated
intricate
interactions
between
microglia
might
provide
potential
therapeutic
targets
prevention
treatment
this
review,
we
examine
specific
open-angle
glaucoma,
including
glaucoma
animal
models,
analyze
interaction
these
two
cell
types.
addition,
discuss
options
based
on
relationship
neurons.
Pharmaceuticals,
Год журнала:
2023,
Номер
16(2), С. 215 - 215
Опубликована: Янв. 31, 2023
Oxidative
stress
is
an
imbalance
between
the
increased
production
of
reactive
species
and
reduced
antioxidant
activity,
which
can
cause
a
variety
disturbances
including
ocular
diseases.
Lycium
barbarum
polysaccharides
(LBPs)
are
complex
isolated
from
fruit
L.
barbarum,
showing
distinct
roles
in
antioxidants.
Moreover,
it
relatively
safe
non-toxic.
In
recent
years,
activities
LBPs
have
attracted
remarkable
attention.
order
to
illustrate
its
significance
underlying
therapeutic
value
for
vision,
we
comprehensively
review
progress
on
mechanisms
LBP
potential
applications
diseases,
diabetic
retinopathy,
hypertensive
neuroretinopathy,
age-related
macular
degeneration,
retinitis
pigmentosa,
retinal
ischemia/reperfusion
injury,
glaucoma,
dry
eye
syndrome,
cataract.