ADAMTS10, a secreted metalloproteinase, is crucial for extracellular matrix (ECM) turnover and is involved in multiple biological processes. It binds to fibrillin microfibrils, promotes their formation, and influences fibrillin isoform composition, playing a role in pathways related to tissue development and homeostasis. Mutations in ADAMTS10 can lead to autosomal recessive Weill-Marchesani Syndrome, characterized by short stature and ocular abnormalities, and also cause glaucoma in dogs [1,2,3,4,5].

In Adamts10 -/- mice, there is reduced viability on the C57BL/6 background, and surviving mice have some features like smaller size and stiff skin. In the eye, zonule fibers are thicker and show persistent fibrillin-2 staining, suggesting fibrillin-2 is a substrate of ADAMTS10. In zebrafish embryos, loss of adamts10 function reduces retinal ganglion cell reporter fluorescence, disrupts the formation of an ordered retinal ganglion cell layer, and reduces constitutive TGFβ signaling in the eye [3,1]. In a mouse model carrying the G661R mutation of ADAMTS10 (ADAMTS10G661R/G661R), there are RGC dysfunction, optic nerve axon structural changes, and increased apoptosis in the retina during postnatal development, accompanied by decreased TGFβ signaling [6].

In conclusion, ADAMTS10 is essential for ECM-related processes, especially in fibrillin microfibril function. Its role in retinal ganglion cell development and glaucoma-related optic neuropathy has been revealed through animal models. The study of ADAMTS10 in KO mouse models contributes to understanding the pathogenesis of Weill-Marchesani Syndrome and glaucoma, providing insights for potential therapeutic strategies.