PMID- 36773475
OWN - NLM
STAT- MEDLINE
DCOM- 20230411
LR  - 20230504
IS  - 1878-5646 (Electronic)
IS  - 0042-6989 (Linking)
VI  - 206
DP  - 2023 May
TI  - Binocular benefit following monocular subretinal AAV injection in a mouse model 
      of autosomal dominant retinitis pigmentosa (adRP).
PG  - 108189
LID - S0042-6989(23)00013-5 [pii]
LID - 10.1016/j.visres.2023.108189 [doi]
AB  - Autosomal dominant retinitis pigmentosa (adRP) is frequently caused by mutations 
      in RHO, the gene for rhodopsin. In previous experiments in dogs with the T4R 
      mutation in RHO, an AAV2/5 vector expressing an shRNA directed to human and dog 
      RHO mRNA and an shRNA-resistant human RHO cDNA (AAV-RHO820-shRNA820) prevented 
      retinal degeneration for more than eight months following injection. It is 
      crucial, however, to determine if this RNA replacement vector acts in a 
      mutation-independent and species-independent manner. We, therefore, injected mice 
      transgenic for human P23H RHO with this vector unilaterally at postnatal day 30. 
      We monitored their retinal structure by using spectral-domain optical coherence 
      tomography (SD-OCT) and retinal function using electroretinography (ERG) for nine 
      months. We compared these to P23H RHO transgenic mice injected unilaterally with 
      a control vector. Though retinas continued to thin over time, compared to control 
      injected eyes, treatment with AAV-RHO820-shRNA820 slowed the loss of 
      photoreceptor cells and the decrease in ERG amplitudes during the nine-month 
      study period. Unexpectedly, we also observed the preservation of retinal 
      structure and function in the untreated contralateral eyes of AAV-RHO820-shRNA820 
      treated mice. PCR analysis and western blots showed that a low amount of vector 
      from injected eyes was present in uninjected eyes. In addition, protective 
      neurotrophic factors bFGF and GDNF were elevated in both eyes of treated mice. 
      Our finding suggests that using this or similar RNA replacement vectors in human 
      gene therapy may provide clinical benefit to both eyes of patients with adRP.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Ahmed, Chulbul M
AU  - Ahmed CM
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, FL, USA.
FAU - Massengill, Michael T
AU  - Massengill MT
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, FL, USA.
FAU - Ildefonso, Cristhian J
AU  - Ildefonso CJ
AD  - Department of Ophthalmology, University of Florida, Gainesville, FL, USA.
FAU - Jalligampala, Archana
AU  - Jalligampala A
AD  - Department of Ophthalmology and Visual Sciences, University of Louisville, 
      Louisville, KY, USA.
FAU - Zhu, Ping
AU  - Zhu P
AD  - Department of Ophthalmology, University of Florida, Gainesville, FL, USA.
FAU - Li, Hong
AU  - Li H
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, FL, USA.
FAU - Patel, Anil P
AU  - Patel AP
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, FL, USA.
FAU - McCall, Maureen A
AU  - McCall MA
AD  - Department of Ophthalmology and Visual Sciences, University of Louisville, 
      Louisville, KY, USA.
FAU - Lewin, Alfred S
AU  - Lewin AS
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, FL, USA. Electronic address: lewin@ufl.edu.
LA  - eng
GR  - F30 EY027163/EY/NEI NIH HHS/United States
GR  - S10 OD028476/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230209
PL  - England
TA  - Vision Res
JT  - Vision research
JID - 0417402
RN  - 9009-81-8 (Rhodopsin)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Dogs
MH  - *Retinitis Pigmentosa/genetics/therapy
MH  - Retina
MH  - Rhodopsin/genetics
MH  - Electroretinography
MH  - Mice, Transgenic
MH  - RNA, Small Interfering
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - AAV
OT  - RNA interference
OT  - Retinitis pigmentosa
OT  - Rhodopsin
COIS- Declaration of Competing Interest The University of Florida holds patents 
      covering the AAV vector used in these experiments, and ASL and MTM may earn 
      royalties due to these patents.
EDAT- 2023/02/12 06:00
MHDA- 2023/04/11 06:42
CRDT- 2023/02/11 18:12
PHST- 2022/12/09 00:00 [received]
PHST- 2023/01/05 00:00 [revised]
PHST- 2023/01/05 00:00 [accepted]
PHST- 2023/04/11 06:42 [medline]
PHST- 2023/02/12 06:00 [pubmed]
PHST- 2023/02/11 18:12 [entrez]
AID - S0042-6989(23)00013-5 [pii]
AID - 10.1016/j.visres.2023.108189 [doi]
PST - ppublish
SO  - Vision Res. 2023 May;206:108189. doi: 10.1016/j.visres.2023.108189. Epub 2023 Feb 
      9.