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Updated: May 19, 2026

Retinal Pathophysiological Evaluation in a Rat Model
Published on: May 6, 2022
Diet-induced obesity impairs AKT signalling in the retina and causes retinal degeneration
Anderson C Marçal1, Mauro Leonelli, Jarlei Fiamoncini
1Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas (ICB), Universidade de São Paulo (USP), SP, Brazil. acmarcal@yahoo.com.br
Abstract:
Retinopathy, a common complication of diabetes, is characterized by an unbalanced production of nitric oxide (NO), a process regulated by nitric oxide synthase (NOS). We hypothesized that retinopathy might stem from changes in the insulin receptor substrate (IRS)/PI3K/AKT pathway and/or expression of NOS isoforms. Thus, we analysed the morphology and apoptosis index in retinas of obese rats in whom insulin resistance had been induced by a high-fat diet (HFD). Immunoblotting analysis revealed that the retinal tissue of HFD rats had lower levels of AKT(1) , eNOS and nNOS protein than those of samples taken from control animals. Furthermore, immunohistochemical analyses indicated higher levels of iNOS and 4-hydroxynonenal and a larger number of apoptotic nuclei in HFD rats. Finally, both the inner and outer retinal layers of HFD rats were thinner than those in their control counterparts. When considered alongside previous results, these patterns suggest two major ways in which HFD might impact animals: direct activity of ingested fatty acids and/or via insulin-resistance-induced changes in intracellular pathways. We discuss these possibilities in further detail and advocate the use of this animal model for further understanding relationships between retinopathy, metabolic syndrome and type 2 diabetes.
Insights
High-fat diets induce insulin resistance, leading to changes in nitric oxide synthase (NOS) and retinal damage. This study in obese rats reveals thinner retinal layers and increased apoptosis, suggesting a link between diet, metabolic syndrome, and retinopathy.
Area of Science:
- Ophthalmology
- Metabolic Science
- Molecular Biology
Background:
- Diabetic retinopathy is linked to nitric oxide (NO) imbalance, regulated by nitric oxide synthase (NOS).
- The insulin receptor substrate (IRS)/PI3K/AKT pathway and NOS isoforms may be involved in retinopathy development.
- Insulin resistance is a key factor in metabolic syndrome and type 2 diabetes.
Purpose of the Study:
- To investigate the impact of high-fat diet (HFD)-induced insulin resistance on retinal morphology and apoptosis.
- To analyze changes in key signaling pathways and NOS isoform expression in the retina of HFD-fed rats.
- To explore the relationship between HFD, insulin resistance, and retinopathy.
Main Methods:
- Induction of insulin resistance in obese rats using a high-fat diet (HFD).
- Morphological and apoptosis index analysis of retinal tissues.
- Immunoblotting to quantify protein levels of AKT(1), eNOS, and nNOS.
- Immunohistochemistry to assess iNOS and 4-hydroxynonenal levels and apoptotic nuclei count.
Main Results:
- HFD rats showed decreased levels of AKT(1), eNOS, and nNOS proteins in retinal tissue.
- Increased levels of iNOS and 4-hydroxynonenal were observed in HFD rats.
- HFD rats exhibited a higher number of apoptotic nuclei and thinner inner and outer retinal layers compared to controls.
Conclusions:
- HFD-induced insulin resistance alters retinal pathways, affecting NOS expression and leading to retinal damage and apoptosis.
- Retinopathy may develop through direct effects of dietary fatty acids or insulin-resistance-mediated intracellular pathway changes.
- This HFD-induced insulin resistance rat model is valuable for studying retinopathy in the context of metabolic syndrome and type 2 diabetes.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
Diabetic Retinopathy
Type II Diabetes II: Pathophysiology
Insulin: The Receptor and Signaling Pathways
Type II Diabetes I: Introduction
