A laser-induced mouse model of progressive retinal degeneration with central sparing displays features of parafoveal geographic atrophy
A laser-induced mouse model of progressive retinal degeneration with central sparing displays features of parafoveal geographic atrophy
There are no disease-modifying treatments available for geographic atrophy (GA), the advanced form of dry age-related macular degeneration. Current murine models fail to fully recapitulate the features of GA and thus hinder drug discovery. Here we describe a novel mouse model of retinal degeneration with hallmark features of GA. We used an 810 nm laser to create a retinal lesion with central sparing (RLCS), simulating parafoveal atrophy observed in patients with progressive GA. Laser-induced RLCS resulted in progressive GA-like pathology with the development of a confluent atrophic lesion. We demonstrate significant changes to the retinal structure and thickness in the central unaffected retina over a 24-week post-laser period, confirmed by longitudinal optical coherence tomography scans. We further show characteristic features of progressive GA, including a gradual reduction in the thickness of the central, unaffected retina and of total retinal thickness. Histological changes observed in the RLCS correspond to GA pathology, which includes the collapse of the outer nuclear layer, increased numbers of GFAP + , CD11b + and FcγRI + cells, and damage to cone and rod photoreceptors. We demonstrate a laser-induced mouse model of parafoveal GA progression, starting at 2 weeks post-laser and reaching confluence at 24 weeks post-laser. This 24-week time-frame in which GA pathology develops, provides an extended window of opportunity for proof-of-concept evaluation of drugs targeting GA. This time period is an added advantage compared to several existing models of geographic atrophy.
Khan, Adnan
97374057-d7e7-4849-ac94-c125ba1cc360
Soundara pandi, Sudha priya P
784c58a0-247a-40a8-b36f-92716605fdf0
Scott, Jennifer A
bdc803de-3082-4727-a4ca-f5a1cf3fcfcc
Sanchez-bretano sanchez, Aida
23183db4-2bd9-42af-9e36-a580e3a52ad1
Lynn, Savannah
de0c4ec2-8a3c-4b16-9e47-ea13abc32a3b
Ratnayaka, J. Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
14 March 2023
Khan, Adnan
97374057-d7e7-4849-ac94-c125ba1cc360
Soundara pandi, Sudha priya P
784c58a0-247a-40a8-b36f-92716605fdf0
Scott, Jennifer A
bdc803de-3082-4727-a4ca-f5a1cf3fcfcc
Sanchez-bretano sanchez, Aida
23183db4-2bd9-42af-9e36-a580e3a52ad1
Lynn, Savannah
de0c4ec2-8a3c-4b16-9e47-ea13abc32a3b
Ratnayaka, J. Arjuna
002499b8-1a9f-45b6-9539-5ac145799dfd
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Khan, Adnan, Soundara pandi, Sudha priya P, Scott, Jennifer A, Sanchez-bretano sanchez, Aida, Lynn, Savannah, Ratnayaka, J. Arjuna, Teeling, Jessica and Lotery, Andrew
(2023)
A laser-induced mouse model of progressive retinal degeneration with central sparing displays features of parafoveal geographic atrophy.
Scientific Reports, 13 (4194), [4194].
(doi:10.1038/s41598-023-31392-3).
Abstract
There are no disease-modifying treatments available for geographic atrophy (GA), the advanced form of dry age-related macular degeneration. Current murine models fail to fully recapitulate the features of GA and thus hinder drug discovery. Here we describe a novel mouse model of retinal degeneration with hallmark features of GA. We used an 810 nm laser to create a retinal lesion with central sparing (RLCS), simulating parafoveal atrophy observed in patients with progressive GA. Laser-induced RLCS resulted in progressive GA-like pathology with the development of a confluent atrophic lesion. We demonstrate significant changes to the retinal structure and thickness in the central unaffected retina over a 24-week post-laser period, confirmed by longitudinal optical coherence tomography scans. We further show characteristic features of progressive GA, including a gradual reduction in the thickness of the central, unaffected retina and of total retinal thickness. Histological changes observed in the RLCS correspond to GA pathology, which includes the collapse of the outer nuclear layer, increased numbers of GFAP + , CD11b + and FcγRI + cells, and damage to cone and rod photoreceptors. We demonstrate a laser-induced mouse model of parafoveal GA progression, starting at 2 weeks post-laser and reaching confluence at 24 weeks post-laser. This 24-week time-frame in which GA pathology develops, provides an extended window of opportunity for proof-of-concept evaluation of drugs targeting GA. This time period is an added advantage compared to several existing models of geographic atrophy.
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Published date: 14 March 2023
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Funding Information:
The authors thank David Chatelet and David Johnston (Biomedical Imaging Unit, University of Southampton) for assistance with imaging and analysis, and the Gift of Sight Appeal for purchasing equipment used in this work.
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© 2023, The Author(s).
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Local EPrints ID: 476186
URI: http://eprints.soton.ac.uk/id/eprint/476186
ISSN: 2045-2322
PURE UUID: 157452ed-d2a7-4791-928f-732affca7b31
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Date deposited: 13 Apr 2023 16:50
Last modified: 17 Mar 2024 03:56
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Author:
Sudha priya P Soundara pandi
Author:
Jennifer A Scott
Author:
Aida Sanchez-bretano sanchez
Author:
Savannah Lynn
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