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Updated: Sep 20, 2025
Quantification of Vascular Parameters in Whole Mount Retinas of Mice with Non-Proliferative and Proliferative Retinopathies
Published on: March 12, 2022
Comprehensive genome-wide analysis of retinal vessel caliber reveals microvascular-blood pressure pathways: advancing
Yongyi Niu1,2, Xue Li3,2, Jingze Guo2,4
1Department of Ophthalmology, Guangdong Provincial People's Hospital of Southern Medical University, Guangzhou, 510080 China.
Insights
This study reveals a causal link between retinal arteriolar caliber and blood pressure, identifying genetic factors and pathways. Findings support personalized medicine for hypertension and related vascular diseases.
Area of Science:
- Genetics and genomics
- Ophthalmology
- Cardiovascular medicine
Background:
- Retinal vessel caliber is linked to systemic blood pressure (BP), but the causal relationship is unclear.
- Understanding this connection is vital for predictive, preventive, and personalized medicine (PPPM) in managing hypertension.
- Hypertension complications pose significant cardiovascular health risks.
Purpose of the Study:
- To investigate genetic factors influencing retinal vessel calibers (CRAE, CRVE, AVR) and their causal relationship with BP traits.
- To identify predictive biomarkers and personalized intervention targets for cardiovascular health.
- To advance PPPM principles in managing hypertension and its sequelae.
Main Methods:
- Genome-wide association study (GWAS) on 36,223 UK Biobank participants of European descent.
- Mendelian randomization analysis and genetic correlation analysis.
- Transcriptomic data analysis to identify causal pathways in vessel tissue.
Main Results:
- GWAS identified significant single nucleotide polymorphisms (SNPs) associated with CRAE, CRVE, and AVR.
- Shared heritability was found between BP traits and CRAE/AVR, but not CRVE.
- Bidirectional causal relationships were confirmed between CRAE and BP traits; CRVE was not causally linked to BP.
Conclusions:
- Elucidated the complex genetic relationship between blood pressure and retinal vessel caliber.
- Highlighted potential intervention targets for lowering BP and addressing vascular narrowing.
- Findings support tailored prevention and treatment strategies for hypertension within PPPM frameworks.
Background:
Retinal vessel caliber is strongly associated with systemic blood pressure (BP); however, the causal relationship between retinal vascular caliber and BP remains unclear. Understanding this relationship is essential for advancing predictive, preventive, and personalized medicine (PPPM) approaches to effectively manage hypertension and its related complications.
Working Hypothesis:
Microvessel morphology is causally related to blood pressure. By integrating genome-wide association studies, Mendelian randomization analysis, transcriptomic data, and multivariate genomic approaches, this study aims to identify predictive biomarkers, uncover preventive strategies, and develop personalized intervention targets, thereby advancing the principles of 3P medicine for improved cardiovascular health management.
Methods And Results:
We conducted a comprehensive investigation into the genetic factors underlying retinal vessel calibers and their complex relationship with BP traits. Our genome-wide association study (GWAS) assess retinal vessel calibers-central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and the arteriole-to-venule ratio (AVR)-in a subset of 36,223 individuals of European descent from the UK Biobank. The analysis identified 9, 5, and 4 SNPs located in TNS, Y_RNA, PBLD, C10orf32-ASMT:AS3MT, GNB3:CDCA3, NTN4, COL4 A2, CTD-2378E21.1, WNT7B, VTA1, FCF1, NPLOC4, FUT1 and CSK region, which are significantly associated with CRAE, CRVE, and AVR, respectively. Genetic correlation analysis revealed shared heritability between BP traits and both CRAE and AVR, but not CRVE. Mendelian randomization analysis confirmed bidirectional causal relationships between CRAE and BP traits, whereas CRVE was neither influenced by nor influenced BP traits. To explore the potential regulatory mechanisms, we leveraged transcriptomic data and identified the following causal pathways in vessel tissue: The expression of MRPL23-AS1 and ULK3 was correlated with the elevation of blood pressure SBP and narrowing of the CRAE. Finally, we constructed a multivariable genetic model including CRAE, AVR, SBP, and DBP, suggesting a common driving factor which underlies these traits.
Conclusions:
Our study elucidates the complex relationship between BP and retinal vessel caliber, highlighting potential intervention targets for lowering BP and vascular narrowing-related diseases. These findings contribute to the development of tailored prevention and treatment strategies aligned with PPPM principles.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s13167-025-00411-w.
