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An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy
Published on: January 25, 2019
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Transcriptomic clock predicts vascular changes of prodromal diabetic retinopathy.
Huishi Toh1, Alexander Smolentsev1, Ryan Sadjadi1
1Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USA.
Scientific Reports
|August 10, 2023
Summary
Early diabetic retinopathy (DR) is poorly understood. This study reveals gene expression patterns linked to acellular capillary density, offering a new way to track DR progression and identify potential drug targets.
Area of Science:
- Ophthalmology
- Genomics
- Diabetology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss in diabetics.
- Early DR pathogenesis remains unclear, hindering timely intervention.
- Acellular capillary density is a key early indicator of DR.
Purpose of the Study:
- To investigate early diabetic retinopathy pathogenesis using transcriptomic analysis.
- To identify biomarkers and therapeutic targets for early DR.
- To develop a predictive model for early DR progression.
Main Methods:
- Whole retinal vascular transcriptomic analysis in a Nile rat model.
- Bayesian networks to model associations between acellular capillary density and risk factors (glucose, diet, sex).
- Segmented regression and random forest models to identify gene expression patterns and predict acellular capillary density.
Main Results:
- Identified gene expression patterns and enriched Gene Ontology terms associated with increased acellular capillary density.
- Developed a 14-gene expression model to predict acellular capillary density, serving as a transcriptomic clock for early DR.
- Uncovered complex interactions between acellular capillary density, blood glucose, diet, and sex.
Conclusions:
- A data-driven approach provides insights into early DR pathogenesis.
- The developed transcriptomic clock can quantify early DR severity.
- Identified NVP-TAE684, geldanamycin, and NVP-AUY922 as potential drugs to attenuate early DR, warranting further investigation.
