Contribution of the Minor Chain Type IV Collagen Network to the Mechanics of the Ocular Lens Capsule

The ocular lens capsule (LC) is a specialized basement membrane which completely surrounds the lens. The LC serves as an attachment point for lens epithelial and fiber cells, controls lens solute and water transport, and makes accommodation possible [1]. It is primarily composed of type IV collagen (65% of dry weight), laminin, nidogen, and proteoglycans, of which type IV collagen is the main-tension resisting element [1,2]. Collagen IV monomers organize into polygonal planar networks resembling chicken wire (Fig.1) [3]. There are six different collagen IV monomers, labeled α₁(IV) to α₆(IV) each produced by a separate gene – COL4A1 to COL4A6. Monomers form triple helical protomers in a highly selective manner. In nature, only three monomer combinations have been discovered: the [α₁(IV)]₂α₂(IV) protomer, referred to as the major chain, is found in all basement membranes; the α₃(IV)α₄(IV)α₅(IV) protomer (minor chain) is found only in few basement membranes including the LC; the [α₅(IV)]₂α₆(IV) protomer is very rare and will not be discussed further. Protomers of the same type assemble with one another to form separate networks which are known to have some differences [4]. For example, the minor chain network is more cross-linked than the major chain network. In a hereditary disease called Alport syndrome, the minor chain network is completely missing in males due to a mutation in the COL4A5 gene (located on the X chromosome) which prevents production of the α₅(IV) monomer. Male Alport syndrome patients have significant ocular manifestations such as anterior lenticonus (protrusion of the lens), cataract, and even lens rupture [5] and they exhibit significant thinning of the LC. Because 1) the minor network is more cross-linked than the major network, 2) its absence affects lens shape, and 3) the LC displays pathological disruptions when it is missing, we theorize that its presence confers additional mechanical strength to the LC. Therefore, the objective of this study is to assess the contribution of the minor chain network to the mechanics of the LC.