Binocular benefit following monocular subretinal AAV injection in a mouse model of autosomal dominant retinitis pigmentosa (adRP)
Vision Research,
Journal Year:
2023,
Volume and Issue:
206, P. 108189 - 108189
Published: Feb. 9, 2023
Autosomal
dominant
retinitis
pigmentosa
(adRP)
is
frequently
caused
by
mutations
in
RHO,
the
gene
for
rhodopsin.
In
previous
experiments
dogs
with
T4R
mutation
an
AAV2/5
vector
expressing
shRNA
directed
to
human
and
dog
RHO
mRNA
shRNA-resistant
cDNA
(AAV-RHO820-shRNA820)
prevented
retinal
degeneration
more
than
eight
months
following
injection.
It
crucial,
however,
determine
if
this
RNA
replacement
acts
a
mutation-independent
species-independent
manner.
We,
therefore,
injected
mice
transgenic
P23H
unilaterally
at
postnatal
day
30.
We
monitored
their
structure
using
spectral-domain
optical
coherence
tomography
(SD-OCT)
function
electroretinography
(ERG)
nine
months.
compared
these
control
vector.
Though
retinas
continued
thin
over
time,
eyes,
treatment
AAV-RHO820-shRNA820
slowed
loss
of
photoreceptor
cells
decrease
ERG
amplitudes
during
nine-month
study
period.
Unexpectedly,
we
also
observed
preservation
untreated
contralateral
eyes
treated
mice.
PCR
analysis
western
blots
showed
that
low
amount
from
was
present
uninjected
eyes.
addition,
protective
neurotrophic
factors
bFGF
GDNF
were
elevated
both
Our
finding
suggests
or
similar
vectors
therapy
may
provide
clinical
benefit
patients
adRP.
Language: Английский
Overview of Retinal Gene Therapy: Current Status and Future Challenges
Cold Spring Harbor Perspectives in Medicine,
Journal Year:
2022,
Volume and Issue:
13(7), P. a041278 - a041278
Published: Nov. 14, 2022
The
success
of
the
first
Food
and
Drug
Administration
(FDA)-
European
Medicines
Agency
(EMA)-approved
gene
therapy
for
genetic
disease,
voretigene
neparovovec-rzyl,
(Luxturna)
has
helped
pave
way
development
retinal
therapies
to
target
other
acquired
forms
blindness.
Gene
trials
are
now
taking
place
in
multiple
continents
numerous
countries,
they
use
several
different
transfer
reagents
("vectors"),
studies
have
used
routes
administration,
strategies
being
tested
interventional
with
promising
results.
future
never
been
brighter
individuals
degeneration.
Here
literature
cited
below,
we
summarize
state-of-the-art
consider
some
questions
challenges
that
lie
ahead.
Language: Английский
Infantile Nystagmus Syndrome—Associated Inherited Retinal Diseases: Perspectives from Gene Therapy Clinical Trials
Life,
Journal Year:
2024,
Volume and Issue:
14(11), P. 1356 - 1356
Published: Oct. 23, 2024
Inherited
retinal
diseases
(IRDs)
are
a
clinically
and
genetically
diverse
group
of
progressive
degenerative
disorders
that
can
result
in
severe
visual
impairment
or
complete
blindness.
Despite
their
predominantly
monogenic
inheritance
patterns,
the
genetic
complexity
over
300
identified
disease-causing
genes
presents
significant
challenge
correlating
clinical
phenotypes
with
genotypes.
Achieving
molecular
diagnosis
is
crucial
for
providing
patients
definitive
diagnostic
clarity
facilitating
access
to
emerging
gene-based
therapies
ongoing
trials.
Recent
advances
next-generation
sequencing
technologies
have
markedly
enhanced
our
ability
identify
defects
leading
IRDs,
thereby
propelling
development
therapies.
The
success
voretigene
neparvovec
(Luxturna),
first
approved
gene
therapy
Language: Английский