Metalloproteinase Adamts16 Is Required for Proper Closure of the Optic Fissure

Area of Science:

• Developmental biology
• Ophthalmology
• Molecular genetics

Background:

• Coloboma is a congenital eye disease resulting from failed optic fissure closure.
• Understanding the molecular mechanisms underlying optic fissure closure is critical for addressing sight-threatening conditions.

Purpose of the Study:

• To investigate the role of Adamts16, a metalloproteinase, in the process of optic fissure closure.
• To elucidate the molecular functions of Adamts16 during eye development.

Main Methods:

• Examined Adamts16 expression in developing mouse and zebrafish eyes using RNA in situ hybridization.
• Utilized morpholino knockdowns in zebrafish to assess adamts16 function.
• Employed immunofluorescent staining, BrdU labeling, TUNEL assays, and high-throughput sequencing to analyze cellular and molecular changes in adamts16-deficient eyes.

Main Results:

• Adamts16 expression was detected at the edges of the closing optic fissure in both species.
• Zebrafish knockdown of adamts16 led to coloboma formation.
• In morphant eyes, basement membrane failed to disassemble, cell proliferation decreased, apoptosis increased, and FGF8 was upregulated.

Conclusions:

• Adamts16 is essential for proper optic fissure closure in zebrafish.
• Adamts16 regulates optic fissure closure by degrading the basement membrane, promoting cell proliferation and survival, and restricting FGF8 expression.
• This study identifies a metalloproteinase involved in optic fissure closure, potentially aiding future research into human coloboma etiology.