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Retinal ablation and altered lens differentiation induced by ocular overexpression of BMP7
Fang Cheng Hung1, Shulei Zhao, Qin Chen
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Abstract:
The alphaA-crystallin promoter was used to target expression of bone morphogenetic protein 7 (BMP7) to lens fiber cells in transgenic mice. Surprisingly, lens-specific expression of BMP7 induced widespread apoptosis and rapid ablation of the neural retina in multiple families. Subsequent to retinal ablation, the lens bow region shifted posteriorly until lens epithelial cells completely enveloped the lens. Lens-specific expression of FGF3 was found to rescue the loss of fiber cell differentiation. Our results show that elevated BMP7 levels can induce rapid retinal degeneration accompanied by disruption of the endogenous ocular system for fiber cell induction.
Insights
Lens-specific expression of bone morphogenetic protein 7 (BMP7) in mice caused severe retinal degeneration. FGF3 expression rescued fiber cell differentiation, revealing BMP7
Area of Science:
- Ophthalmology
- Developmental Biology
- Genetics
Background:
- The precise molecular mechanisms regulating ocular development and cell differentiation are crucial for maintaining vision.
- Bone morphogenetic protein 7 (BMP7) is a signaling molecule implicated in various developmental processes, but its specific role in the adult lens and retina requires further elucidation.
Purpose of the Study:
- To investigate the consequences of targeted lens-specific expression of bone morphogenetic protein 7 (BMP7) in transgenic mice.
- To understand the impact of BMP7 on neural retina integrity and lens fiber cell differentiation.
Main Methods:
- Generation of transgenic mice with alphaA-crystallin promoter-driven BMP7 expression specifically in lens fiber cells.
- Histological analysis to assess retinal apoptosis, ablation, and cellular morphology.
- Evaluation of lens epithelial cell migration and differentiation markers.
Main Results:
- Unexpectedly, lens-specific BMP7 expression led to widespread apoptosis and rapid degeneration of the neural retina.
- Retinal ablation resulted in posterior migration of the lens bow and complete envelopment of the lens by epithelial cells.
- Co-expression of FGF3 in the lens rescued the loss of fiber cell differentiation, mitigating some effects of BMP7.
Conclusions:
- Elevated BMP7 levels in the lens can induce rapid retinal degeneration and disrupt the endogenous system for fiber cell induction.
- BMP7 plays a critical role in maintaining retinal integrity and its dysregulation has severe ocular consequences.
- FGF3 shows potential as a therapeutic target for rescuing fiber cell differentiation in the context of BMP7-induced ocular disruption.