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Corneal Vascularization Associated With a Novel PDGFRB Variant
Titas Gladkauskas1, Ove Bruland2, Leen Abu Safieh3,4
1Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Investigative Ophthalmology & Visual Science
|November 7, 2023
Summary
A novel platelet-derived growth factor receptor beta (PDGFRB) variant causes aggressive corneal vascularization. This genetic mutation leads to overactive PDGFRB signaling, but tyrosine kinase inhibitors show promise for targeted treatment.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- Corneal vascularization is a significant cause of vision impairment.
- The genetic underpinnings of aggressive corneal vascularization in children are not well understood.
- Identifying genetic causes can lead to targeted therapeutic strategies.
Purpose of the Study:
- To identify the genetic cause of aggressive corneal vascularization in a family.
- To investigate the molecular consequences of the identified genetic variant.
- To explore potential therapeutic implications of the findings.
Main Methods:
- Exome sequencing was performed on affected individuals.
- HeLa cells were engineered to express either the wild-type or variant PDGFRB (c.1643C>A, p.(Ser548Tyr)).
- ELISA, immunoblot analysis, and sensitivity assays with tyrosine kinase inhibitors (TKIs) were employed.
Main Results:
- A novel PDGFRB variant (c.1643C>A, p.(Ser548Tyr)) was identified in affected family members.
- Cells expressing the variant PDGFRB showed normal baseline phosphorylation but excessive activation upon ligand stimulation.
- The variant PDGFRB was effectively inhibited by several TKIs in vitro.
Conclusions:
- A novel PDGFRB variant is associated with isolated corneal vascularization.
- The variant leads to overactivation of PDGF-PDGFRβ signaling, potentially causing abnormal corneal wound healing.
- Targeted inhibition of PDGFRB with TKIs presents a potential therapeutic avenue for affected patients.
