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Published on: April 2, 2021
Associations between VEGF isoforms and impending retinopathy of prematurity
Tammy Z Movsas1,2, Arivalagan Muthusamy1
1Zietchick Research Institute (ZRI), Plymouth, MI, USA.
Insights
Investigating Vascular Endothelial Growth Factor (VEGF) isoforms in preterm infants revealed distinct correlations between VEGF165 and VEGF121 in males and females. These correlations may predict the development of retinopathy of prematurity (ROP).
Area of Science:
- Neuroscience
- Developmental Biology
- Ophthalmology
Background:
- Vascular Endothelial Growth Factor (VEGF) drives angiogenesis in brain and retina development.
- VEGF165 and VEGF121 are key human VEGF isoforms.
- Dysregulation of VEGF is linked to retinopathy of prematurity (ROP), a neuroretinal disorder, but isoform interactions are unclear.
Purpose of the Study:
- To investigate the correlation between VEGF165 and VEGF121 in preterm infants.
- To determine if specific VEGF isoform correlations precede the diagnosis of non-proliferative retinopathy of prematurity (NP-ROP).
- To test the hypothesis that a specific VEGF165/VEGF121 ratio is associated with normal retinal development, while an altered ratio is linked to ROP.
Main Methods:
- A case/control study was conducted using dried blood spots (DBS) from 65 preterm infants.
- VEGF165 levels were measured using the Mesoscale Discovery Platform.
- VEGF121 levels were quantified via Cloud Clone Elisa Assay.
Main Results:
- In infants with NP-ROP, VEGF165 levels were significantly higher in males compared to females.
- A significant correlation between VEGF165 and VEGF121 was observed in females without ROP, but not in males.
- Conversely, in infants with NP-ROP, a significant correlation existed between VEGF165 and VEGF121 in males, but not in females.
Conclusions:
- Early assessment of VEGF isoform interactions (<1 week after birth) may be crucial for understanding ROP development.
- Retinal angiogenesis may not be a sex-neutral process, as suggested by sex-specific correlations.
- Prospective studies are required to validate these novel findings on VEGF isoform interplay in ROP.
Background/Objective:
Vascular Endothelial Growth Factor (VEGF) is the main driver of angiogenesis during neurodevelopment (i.e., brain and retina). VEGF165 and VEGF121 are the two most prevalent human VEGF isoforms. Although retinopathy of prematurity (ROP), a neuroretinal disorder, is associated with VEGF dysregulation, little is known about the interaction of VEGF isoforms on neuroretinal angiogenesis. We hypothesized that: (a) A specific VEGF165/VEGF121 correlation, at a given time point, is associated with normal retinal development (no ROP) and (b) An altered correlation, of such, is associated with aberrant retinal development (ROP). Utilizing pre-collected dried blood spots (DBS) from <1-week-old preterm infants, we aimed to determine whether correlations between VEGF165 and VEGF121 precede the diagnosis of early stage, non-proliferative ROP (NP-ROP).
Methodology:
We conducted a case/control study, utilizing DBS from 65 preterm infants. We measured DBS levels of VEGF165 on the Mesoscale Discovery Platform and VEGF121 via Cloud Clone Elisa Assay.
Results:
In infants with NP-ROP, VEGF165 is significantly higher in males (than females). In infants without ROP, there is a significant correlation between VEGF165 and VEGF121 in females (but not males). In infants with NP-ROP, the opposite is so; there is a significant correlation between VEGF165 and VEGF121 in males (but not females).
Conclusions:
This pilot study, utilizing de-identified data, suggests the potential importance of examining interactions between VEGF isoforms, at <1 week after birth, to better understand ROP development. Our study also suggests that retinal angiogenesis may not be a sex-neutral process. A prospective study is needed to confirm our novel findings.
