What VEGFR-2 and Adropin Reveal About This Sight-Threatening Condition
The secret to preserving your eyesight might be found in a simple blood test.
Age-related macular degeneration (AMD) is a leading cause of vision loss for people over 50, affecting millions worldwide. As the population ages, understanding this complex disease becomes increasingly urgent. While the role of specific proteins like VEGF in AMD is well-established, scientists are now investigating two new promising players in the bloodstream: vascular endothelial growth factor receptor-2 (VEGFR-2) and a recently discovered peptide called adropin. This article explores how these two circulating molecules might hold the key to better understanding, and potentially treating, this sight-threatening condition.
The more common form, characterized by the buildup of drusen (yellow deposits) and gradual breakdown of light-sensitive cells in the macula.
More CommonThe more severe form, where abnormal blood vessels grow under the retina and leak fluid and blood, causing rapid vision damage.
More SevereThe vascular endothelial growth factor (VEGF) pathway is crucial to wet AMD. VEGF is a signaling protein that stimulates new blood vessel formation. Its primary receptor, VEGFR-2, is responsible for executing most of VEGF's effects, including the harmful angiogenesis and vascular leakage seen in wet AMD 1 8 .
Adropin, discovered only in 2008, is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene. It is primarily produced in the liver and brain but is also found in endothelial cells and other tissues 2 . Initially studied for its roles in glucose and lipid metabolism, researchers have uncovered its broader functions in vascular health. Adropin helps protect blood vessels by promoting the production of nitric oxide, which relaxes vessels and improves blood flow. It also regulates lipid accumulation in specialized cells, including those in the retina 1 5 .
Scientists are particularly interested in whether measuring the levels of VEGFR-2 and adropin in blood serum could serve as useful biomarkers—objective indicators of a disease's presence, severity, or progression.
The investigation into VEGFR-2 and adropin in AMD reveals how scientific understanding often evolves through seemingly contradictory results. Two key studies highlight this process.
A cross-sectional study conducted at JIPMER hospital in India compared 39 AMD patients with 39 diabetic patients without AMD 1 .
| Parameter | AMD Patients | Control Group | P-value |
|---|---|---|---|
| Age (years) | 62.00 (52.00-73.00) | 62.00 (54.00-71.00) | 0.886 |
| Systolic BP (mmHg) | 120.00 (110.00-120.00) | 130.00 (120.00-130.00) | 0.002* |
| Fasting Blood Glucose (mg/dL) | 141.00 (95.00-224.00) | 193.00 (151.00-254.00) | 0.017* |
*Data presented as median with interquartile range; * statistically significant 1
A more recent case-control study from Iran took a different approach, comparing 45 wet AMD patients with 45 healthy controls while strictly excluding individuals with comorbidities like diabetes and hypertension 5 .
| Parameter | Wet AMD Patients | Control Group | P-value |
|---|---|---|---|
| Serum Adropin Level | Significantly Lower | Higher | < 0.001 |
| hs-CRP | Significantly Higher | Lower | 0.031 |
| HDL | Significantly Higher | Lower | < 0.001 |
| Fasting Blood Sugar | No significant difference | No significant difference | 0.097 |
These conflicting results demonstrate the complexity of biomarker research. The different findings may stem from variations in study design, particularly the inclusion criteria—the JIPMER study used diabetic patients as controls, while the Tabriz study used healthy controls and excluded comorbidities. This suggests that underlying metabolic conditions might independently affect adropin levels, potentially masking its relationship with AMD.
To conduct this type of research, scientists rely on specialized laboratory tools. Here are some key reagents used in studying VEGFR-2 and adropin:
| Tool | Function | Example Product |
|---|---|---|
| ELISA Kits | Measure protein concentrations in biological samples like serum or plasma | Human Adropin ELISA Kit 3 , Human VEGFR2 Quantikine ELISA Kit 6 |
| Antibody Sampler Kits | Detect proteins and their activated forms in laboratory samples | Phospho-VEGF Receptor 2 Antibody Sampler Kit 4 |
| Specific Antibodies | Identify and measure specific proteins in various experimental applications | Adropin Antibody for Western Blot 7 |
Research into circulating biomarkers reinforces that AMD is not just an isolated eye condition but a systemic disease with body-wide manifestations. The connection between adropin and both AMD and other conditions is particularly revealing:
Adropin levels decrease with age and are influenced by diet composition, particularly fat and carbohydrate intake 2 .
Adropin promotes endothelial nitric oxide synthase activity, improving vascular function 2 .
Progressive decline in adropin correlates with worsening renal function and glycemic control .
Adropin appears to play a role in modulating inflammation and immune responses 2 .
Adropin promotes endothelial nitric oxide synthase activity, improving vascular function 2 .
These connections might explain why systemic conditions like diabetes and hypertension are risk factors for AMD. They also highlight adropin's potential role as a bridge between metabolic health and eye disease.
The investigation into serum VEGFR-2 and adropin in age-related macular degeneration represents an exciting frontier in ophthalmology research. While questions remain—as evidenced by the conflicting study results—the potential is significant.
Shows promise as a marker for disease severity in AMD, consistent with its established role in VEGF signaling pathways.
Appears to be significantly lower in wet AMD patients without other metabolic comorbidities, suggesting it may serve as a valuable biomarker.
Patient selection and controlling for comorbidities critically influence study outcomes in this field.
Future research with larger sample sizes, longitudinal designs, and more diverse populations will help clarify the relationship between these circulating factors and AMD progression. If validated, these biomarkers could lead to earlier detection methods, better risk stratification, and potentially new therapeutic approaches for preserving vision in millions affected by this debilitating condition.
The journey from laboratory discovery to clinical application is often long and winding, but each study—whether confirming or contradicting previous findings—brings us closer to understanding the complex puzzle of age-related macular degeneration.