PURPOSE: The zonule of Zinn (ciliary zonule) is a system of fibers that centers 
the crystalline lens on the optical axis of the eye. Mutations in zonule 
components underlie syndromic conditions associated with a broad range of ocular 
pathologies, including microspherophakia and ectopia lentis. Here, we used 
HPLC-mass spectrometry to determine the molecular composition of the zonule.
METHODS: Tryptic digests of human and bovine zonular samples were analyzed by 
HPLC-mass spectrometry. The distribution of selected components was confirmed by 
immunofluorescence confocal microscopy. In bovine samples, the composition of 
the equatorial zonule was compared to that of the hyaloid zonule and vitreous 
humor.
RESULTS: The 52 proteins common to the zonules of both species accounted for 
>95% of the zonular protein. Glycoproteins constituted the main structural 
components, with two proteins, FBN1 and LTBP2, constituting 70%-80% of the 
protein. Other abundant components were MFAP2, EMILIN-1, and ADAMTSL-6. Lysyl 
oxidase-like 1, a crosslinking enzyme implicated in collagen and elastin 
biogenesis, was detected at significant levels. The equatorial and hyaloid 
zonular samples were compositionally similar to each other, although the hyaloid 
sample was relatively enriched in the proteoglycan opticin and the fibrillar 
collagens COL2A1, COL11A1, COL5A2, and COL5A3.
CONCLUSIONS: The zonular proteome was surprisingly complex. In addition to 
structural components, it contained signaling proteins, protease inhibitors, and 
crosslinking enzymes. The equatorial and hyaloid zonules were similar in 
composition, but the latter may form part of a composite structure, the hyaloid 
membrane, that stabilizes the vitreous face.