Comparative Analysis of Molecular Landscape in Mouse Models and Patients Reveals Conserved Inflammation Pathways in Age-Related Macular Degeneration.
Invest Ophthalmol Vis Sci
; 65(1): 13, 2024 Jan 02.
Article
in En
| MEDLINE
| ID: mdl-38175639
ABSTRACT
Purpose:
The purpose of this study was to identify key genes and their regulatory networks that are conserved in mouse models of age-related macular degeneration (AMD) and human AMD.Methods:
Retinal RNA-Seq was performed in laser-induced choroidal neovascularization (CNV) mice at day 3 and day 7 after photocoagulation. Mass spectrometry-based proteomic analysis was performed with retinas collected at day 3. Retinal RNA-Seq data was further compared among mouse models of laser-induced CNV and NaIO3-induced retinal degeneration (RD) and a large AMD cohort.Results:
Retinal RNA-Seq revealed upregulated genes and pathways related to innate immunity and inflammation in mice with CNV, with more profound changes at the early stage (day 3). Proteomic analysis further validated these differentially expressed genes and their networks in retinal inflammation during CNV. Notably, the most evident overlap in the retina of mice with laser-induced CNV and NaIO3-induced RD was the upregulation of inflammation-related genes, pointing to a common vital role of retinal inflammation in the early stage for both mouse AMD models. Further comparative transcriptomic analysis of the mouse AMD models and human AMD identified 48 conserved genes mainly involved in inflammation response. Among them, B2M, C3, and SERPING1 were upregulated in all stages of human AMD and the mouse AMD models compared to controls.Conclusions:
Our study demonstrates conserved molecular changes related to retinal inflammation in mouse AMD models and human AMD and provides new insight into the translational application of these mouse models in studying AMD mechanisms and treatments.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Retinal Degeneration
/
Choroidal Neovascularization
/
Macular Degeneration
Limits:
Animals
/
Humans
Language:
En
Journal:
Invest Ophthalmol Vis Sci
/
Investig. ophthalmol. vis. sci. (Online)
/
Investigative ophthalmology & visual science (Online)
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos