Related Experiment Video
Updated: Sep 22, 2025
07:41
Behavioral Assessment of Visual Function via Optomotor Response and Cognitive Function via Y-Maze in Diabetic Rats
Published on: October 23, 2020
6.0K
Neuronal Dysfunction Is Linked to the Famine-Associated Risk of Proliferative Retinopathy in Patients With Type 2
Olena Fedotkina1, Ruchi Jain2, Rashmi B Prasad2
1Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway.
Frontiers in Neuroscience
|May 23, 2022
Summary
Individuals with type 2 diabetes exposed to famine in utero show higher risks of proliferative diabetic retinopathy (PDR). Genetic links to ADRA2A may explain this increased risk, suggesting neuroprotective treatments for PDR.
Area of Science:
- Endocrinology
- Genetics
- Ophthalmology
Background:
- Individuals with type 2 diabetes (T2D) born during famine periods exhibit a disproportionately high risk of vision-threatening proliferative diabetic retinopathy (PDR).
- The specific molecular mechanisms linking intrauterine famine exposure to PDR development remain largely unknown.
Purpose of the Study:
- To investigate potential molecular factors, specifically genetic variants, that contribute to the progression of PDR in individuals with T2D exposed to famine during development.
- To explore the association between single nucleotide polymorphisms (SNPs) and PDR risk under intrauterine famine exposure.
Main Methods:
- Analyzed SNPs previously associated with T2D, glucose metabolism, and pharmacogenetics in a Ukrainian cohort (DOLCE study, n=3,583) with famine exposure history (Great Ukrainian Holodomor).
- Validated top genetic findings in a Hong Kong cohort (HKDR, n=730) with famine exposure history (Japanese invasion WWII).
- Exposed embryonic retinal cells to glucose starvation to mimic famine conditions and assessed gene expression (Adra2a, Pcsk9, Prox1) and neurite outgrowth.
Main Results:
- In the DOLCE study, genetic variants in ADRA2A, PCSK9, and CYP2C19*2 were associated with elevated PDR risk, while PROX1 variants showed reduced risk.
- The association between ADRA2A variants and advanced diabetic retinopathy risk in famine-exposed individuals was replicated in the HKDR cohort.
- In vitro, glucose starvation increased Adra2a and Pcsk9 expression, decreased Prox1 expression, and inhibited neurite outgrowth, indicating lasting effects.
Conclusions:
- Consistent genetic findings link ADRA2A variants to famine-associated PDR risk, suggesting that nerve signaling pathways may mediate the effects of perinatal famine exposure on elevated PDR risk in adults.
- These results highlight the potential of neuroprotective drugs for PDR prevention and treatment.
Related Concept Videos
01:22Diabetes Mellitus: Type 2 and Gestational
3.0K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
3.0K
01:20Pathophysiology of Diabetes
1.3K
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
1.3K
01:19Psychoneuroimmunology: Diabetes and Cancer
72
Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
72
01:22Photoreceptors and Visual Pathways
6.5K
At the molecular level, visual signals trigger transformations in photopigment molecules, resulting in changes in the photoreceptor cell's membrane potential. The photon's energy level is denoted by its wavelength, with each specific wavelength of visible light associated with a distinct color. The spectral range of visible light, classified as electromagnetic radiation, spans from 380 to 720 nm. Electromagnetic radiation wavelengths exceeding 720 nm fall under the infrared category,...
6.5K
01:22Diabetes Mellitus: Overview and Type I Subtype
3.3K
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
3.3K
01:15Diabetes: Symptoms, Diagnosis, and Complications
726
For most patients, experiencing several weeks of polyuria, polydipsia, fatigue, and significant weight loss may indicate the presence of diabetes. Furthermore, adults displaying the phenotypic appearance of type 2 diabetes (particularly those who are obese and not initially insulin-requiring), may have islet cell autoantibodies, suggesting autoimmune-mediated β cell destruction and a diagnosis of latent autoimmune diabetes of adults (LADA). The categorization of glucose homeostasis is...
726