Dysfunction of Calcyphosine-Like gene impairs retinal angiogenesis through the MYC axis and is associated with familial exudative vitreoretinopathy.
The study identifies CAPSL as a potential genetic factor in familial exudative vitreoretinopathy, affecting endothelial cell function and MYC signaling, but does not provide direct clinical implications.
Where it sits
this study against the rest of the igf-1 lr3 (long r3 igf-1) corpusSummary and findings
This study investigates the role of the calcyphosine-like gene (CAPSL) in familial exudative vitreoretinopathy (FEVR), a genetic disorder affecting retinal vascularization. Variants in CAPSL were found to impair endothelial cell function, leading to delayed vascular progression and other cellular impairments. The study identifies CAPSL as a candidate gene for FEVR and suggests its involvement in the MYC signaling pathway.
Abstract
Familial exudative vitreoretinopathy (FEVR) is a severe genetic disorder characterized by incomplete vascularization of the peripheral retina and associated symptoms that can lead to vision loss. However, the underlying genetic causes of approximately 50% of FEVR cases remain unknown. Here, we report two heterozygous variants in calcyphosine-like gene (<i>CAPSL</i>) that is associated with FEVR. Both variants exhibited compromised CAPSL protein expression. Vascular endothelial cell (EC)-specific inactivation of <i>Capsl</i> resulted in delayed radial/vertical vascular progression, compromised endothelial proliferation/migration, recapitulating the human FEVR phenotypes. <i>CAPSL</i>-depleted human retinal microvascular endothelial cells (HRECs) exhibited impaired tube formation, decreased cell proliferation, disrupted cell polarity establishment, and filopodia/lamellipodia formation, as well as disrupted collective cell migration. Transcriptomic and proteomic profiling revealed that <i>CAPSL</i> abolition inhibited the MYC signaling axis, in which the expression of core MYC targeted genes were profoundly decreased. Furthermore, a combined analysis of <i>CAPSL</i>-depleted HRECs and <i>c-MYC</i>-depleted human umbilical vein endothelial cells uncovered similar transcription patterns. Collectively, this study reports a novel FEVR-associated candidate gene, <i>CAPSL</i>, which provides valuable information for genetic counseling of FEVR. This study also reveals that compromised CAPSL function may cause FEVR through MYC axis, shedding light on the potential involvement of MYC signaling in the pathogenesis of FEVR.
Background
The paper addresses the biological question of how the dysfunction of the Calcyphosine-Like gene affects retinal angiogenesis, particularly in the context of familial exudative vitreoretinopathy. Prior research has indicated the importance of angiogenesis in retinal diseases, but the specific mechanisms involving the MYC axis remain unclear. This study aims to elucidate these mechanisms and their potential implications for understanding retinal pathologies.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Key findings
- Not reported in abstract.
- Not reported in abstract.
- Not reported in abstract.
Limitations
- Not reported in abstract.
- Not reported in abstract.