Loxl1, or lysyl oxidase-like 1, is a matrix cross-linking enzyme crucial for elastic fiber formation [1,2]. It may be involved in multiple biological processes, and its associated pathways likely relate to extracellular matrix remodeling. Genetic models, such as gene-edited zebrafish, can be valuable for studying its functions [2].

In zebrafish, loxl1 deficiency caused zonular bundling disorders in juveniles and accumulation of pearl-like particles in adults, along with thinning or loss of the elastic lamina in Bruch's membrane, mimicking some ocular manifestations of exfoliation syndrome (XFS) [2]. In human studies, certain genetic variants of LOXL1 confer risk for XFS, but are not the sole causative factor as many genetically affected individuals do not develop the disease or subsequent glaucoma (XFG) [1]. In XFG patient-derived cells, LOXL1 protein undergoes autophagic clearance, suggesting aggregation [1].

In conclusion, Loxl1 is essential for elastic fiber formation and is implicated in XFS. The loxl1-deficient zebrafish model provides insights into the role of Loxl1 in XFS-related ocular pathologies, highlighting its significance in understanding the disease mechanism.

References:

1. Bernstein, Audrey M, Ritch, Robert, Wolosin, J Mario. 2019. LOXL1 folding in exfoliation glaucoma. In Advances in protein chemistry and structural biology, 118, 273-288. doi:10.1016/bs.apcsb.2019.09.005. https://pubmed.ncbi.nlm.nih.gov/31928728/

2. Zhang, Min, Sun, Shaoyang, Wang, Lei, Chen, Zexu, Jiang, Yongxiang. 2021. Zonular defects in loxl1-deficient zebrafish. In Clinical & experimental ophthalmology, 50, 62-73. doi:10.1111/ceo.14017. https://pubmed.ncbi.nlm.nih.gov/34585825/