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Published on: March 12, 2022
Pro- and antiangiogenic VEGF and its receptor status for the severity of diabetic retinopathy
Suman K Paine1, Lakshmi K Mondal2, Prasanta K Borah1
1Regional Medical Research Centre-NE Region (Indian Council of Medical Research), Assam, India.
Purpose:
Alteration of pro- and antiangiogenic homeostasis of vascular endothelial growth factor (VEGF) isoforms in patients with hyperglycemia seems crucial but substantially unexplored at least quantitatively for diabetic retinopathy (DR). Therefore, in the present study we aimed to estimate the difference between the pro- (VEGF165a) and antiangiogenic (VEGF165b) VEGF isoforms and its soluble receptors for severity of DR.
Methods:
The study included 123 participants (diabetic retinopathy: 81, diabetic control: 20, non-diabetic control: 22) from the Regional Institute of Ophthalmology, Kolkata. The protein levels of VEGF165a (proangiogenic), VEGF165b (antiangiogenic), VEGF receptor 1 (VEGFR1), VEGFR2, and VEGFR3 in plasma were determined with enzyme-linked immunosorbent assay (ELISA).
Results:
An imbalance in VEGF homeostasis, a statistically significant concomitant increase (p<0.0001) in the level of VEGF165a and a decrease in the level of VEGF165b, was observed with the severity of the disease. Increased differences between VEGF165a and VEGF165b i.e. VEGF165a-b concomitantly increased statistically significantly with the severity of the disease (p<0.0001), patients with diffuse diabetic macular edema (DME) with proliferative DR (PDR) had the highest imbalance. The plasma soluble form of VEGFR2 concentration consistently increased statistically significantly with the severity of the disease (p<0.0001).
Conclusions:
The increased difference or imbalance between the pro- (VEGF165a) and antiangiogenic (VEGF165b) homeostasis of the VEGF isoforms, seems crucial for an adverse prognosis of DR and may be a better explanatory marker compared with either VEGF isoform.
Insights
The balance of vascular endothelial growth factor (VEGF) isoforms is altered in diabetic retinopathy (DR). An increased difference between proangiogenic VEGF165a and antiangiogenic VEGF165b correlates with DR severity.
Area of Science:
- Ophthalmology
- Angiogenesis Research
- Diabetic Complications
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss.
- The role of vascular endothelial growth factor (VEGF) isoforms in DR pathogenesis is not fully understood.
- Hyperglycemia may disrupt the balance of pro- and antiangiogenic VEGF isoforms.
Purpose of the Study:
- To quantitatively assess the difference between proangiogenic (VEGF165a) and antiangiogenic (VEGF165b) VEGF isoforms.
- To evaluate the relationship between VEGF isoform imbalance and DR severity.
- To investigate soluble VEGF receptors in relation to DR.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma levels of VEGF165a, VEGF165b, VEGFR1, VEGFR2, and VEGFR3.
- 123 participants were included: 81 with DR, 20 with diabetes but no DR, and 22 non-diabetic controls.
- Protein levels were correlated with DR severity.
Main Results:
- A significant increase in VEGF165a and decrease in VEGF165b was observed with increasing DR severity (p<0.0001).
- The difference (VEGF165a-b) significantly increased with DR severity, highest in proliferative DR with diabetic macular edema.
- Soluble VEGFR2 levels also significantly increased with DR severity (p<0.0001).
Conclusions:
- An imbalance favoring proangiogenic VEGF165a over antiangiogenic VEGF165b is crucial in DR progression.
- The VEGF isoform imbalance may serve as a more effective prognostic marker for DR than individual isoforms.
- VEGF homeostasis disruption is a key factor in adverse DR outcomes.
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