PMID- 38252153
OWN - NLM
STAT- MEDLINE
DCOM- 20240205
LR  - 20240205
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Print)
IS  - 1420-682X (Linking)
VI  - 81
IP  - 1
DP  - 2024 Jan 22
TI  - Combination of blockade of endothelin signalling and compensation of IGF1 
      expression protects the retina from degeneration.
PG  - 51
LID - 10.1007/s00018-023-05087-x [doi]
LID - 51
AB  - Retinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal 
      dysfunction, affecting 1 in 4000 people worldwide. This disease is currently 
      assumed to be intractable, because effective therapeutic methods have not been 
      established, regardless of genetic or sporadic traits. Here, we examined a RP 
      mouse model in which the Prominin-1 (Prom1) gene was deficient and investigated 
      the molecular events occurring at the outset of retinal dysfunction. We extracted 
      the Prom1-deficient retina subjected to light exposure for a short time, 
      conducted single-cell expression profiling, and compared the gene expression with 
      and without stimuli. We identified the cells and genes whose expression levels 
      change directly in response to light stimuli. Among the genes altered by light 
      stimulation, Igf1 was decreased in rod photoreceptor cells and astrocytes under 
      the light-stimulated condition. Consistently, the insulin-like growth factor 
      (IGF) signal was weakened in light-stimulated photoreceptor cells. The recovery 
      of Igf1 expression with the adeno-associated virus (AAV) prevented photoreceptor 
      cell death, and its treatment in combination with the endothelin receptor 
      antagonist led to the blockade of abnormal glial activation and the promotion of 
      glycolysis, thereby resulting in the improvement of retinal functions, as assayed 
      by electroretinography. We additionally demonstrated that the attenuation of 
      mammalian/mechanistic target of rapamycin (mTOR), which mediates IGF signalling, 
      leads to complications in maintaining retinal homeostasis. Together, we propose 
      that combinatorial manipulation of distinct mechanisms is useful for the 
      maintenance of the retinal condition.
CI  - (c) 2024. The Author(s).
FAU - Shigesada, Naoya
AU  - Shigesada N
AD  - Division of Biological Science, Nara Institute of Science and Technology, Ikoma, 
      630-0192, Japan.
FAU - Shikada, Naoya
AU  - Shikada N
AD  - Division of Biological Science, Nara Institute of Science and Technology, Ikoma, 
      630-0192, Japan.
FAU - Shirai, Manabu
AU  - Shirai M
AD  - Omics Research Center (ORC), National Cerebral and Cardiovascular Center, Suita, 
      Osaka, 564-8565, Japan.
FAU - Toriyama, Michinori
AU  - Toriyama M
AD  - Department of Biomedical Chemistry, School of Science and Technology, Kwansei 
      Gakuin University, Sanda, 669-1337, Japan.
FAU - Higashijima, Fumiaki
AU  - Higashijima F
AD  - Department of Ophthalmology, Graduate School of Medicine, Yamaguchi University, 
      Ube, 755-0046, Japan.
FAU - Kimura, Kazuhiro
AU  - Kimura K
AD  - Department of Ophthalmology, Graduate School of Medicine, Yamaguchi University, 
      Ube, 755-0046, Japan.
FAU - Kondo, Toru
AU  - Kondo T
AD  - Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido 
      University, Sapporo, 060-0815, Japan.
FAU - Bessho, Yasumasa
AU  - Bessho Y
AD  - Division of Biological Science, Nara Institute of Science and Technology, Ikoma, 
      630-0192, Japan.
FAU - Shinozuka, Takuma
AU  - Shinozuka T
AD  - Division of Biological Science, Nara Institute of Science and Technology, Ikoma, 
      630-0192, Japan.
FAU - Sasai, Noriaki
AU  - Sasai N
AUID- ORCID: 0000-0003-0360-1138
AD  - Division of Biological Science, Nara Institute of Science and Technology, Ikoma, 
      630-0192, Japan. noriakisasai@bs.naist.jp.
LA  - eng
GR  - 21H02886/Japan Society for the Promotion of Science/
GR  - 23H02677/Japan Society for the Promotion of Science/
GR  - 23K14196/Japan Society for the Promotion of Science/
GR  - 20H03263/Japan Society for the Promotion of Science/
GR  - 20H05036/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20240122
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (Endothelins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 0 (insulin-like growth factor-1, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Endothelins
MH  - Insulin-Like Growth Factor I/genetics
MH  - *Macular Degeneration
MH  - Retina
MH  - *Retinal Diseases
MH  - Retinal Rod Photoreceptor Cells
MH  - *Retinitis Pigmentosa
PMC - PMC10803390
OTO - NOTNLM
OT  - Adeno-associated virus (AAV)
OT  - Gliosis
OT  - Insulin-like growth factor (IGF)
OT  - Mammalian/mechanical target of rapamycin (mTOR)
OT  - Prominin-1
OT  - Retinitis pigmentosa
OT  - Single-cell RNA sequencing (scRNA-seq)
COIS- The authors declare that no competing interests exist.
EDAT- 2024/01/22 12:42
MHDA- 2024/01/23 06:43
PMCR- 2024/01/22
CRDT- 2024/01/22 11:05
PHST- 2023/07/22 00:00 [received]
PHST- 2023/12/12 00:00 [accepted]
PHST- 2023/12/01 00:00 [revised]
PHST- 2024/01/23 06:43 [medline]
PHST- 2024/01/22 12:42 [pubmed]
PHST- 2024/01/22 11:05 [entrez]
PHST- 2024/01/22 00:00 [pmc-release]
AID - 10.1007/s00018-023-05087-x [pii]
AID - 5087 [pii]
AID - 10.1007/s00018-023-05087-x [doi]
PST - epublish
SO  - Cell Mol Life Sci. 2024 Jan 22;81(1):51. doi: 10.1007/s00018-023-05087-x.