Developmentally regulated appearance of spliced variants of type XII collagen in the cornea

PURPOSE. TO determine whether temporal and spatial changes in the distribut ion of the long and short alternatively spliced variants of type XII collag en are associated with any specific morphogenetic events in pre- and postna tal development of the cornea and surrounding tissues. METHODS. The distribution of alternatively spliced variants of type XII col lagen in fetal and newborn rabbit tissues was analyzed immunohistochemicall y using monoclonal antibodies that recognize either only the long form or b oth the short and the long forms of type XII collagen. RESULTS. During early fetal development of the cornea in rabbit (days 14 - 17), the short form of type XII collagen was detected in the corneal stroma , the sclera, and the stroma in the rudimentary eyelid folds, whereas the l ong form was present only in the sclera. The long form was first evident in the cornea at day 24 but only in the posterior stroma. At later stages of prenatal development, the distribution of the long variant gradually extend ed toward the anterior stroma and in the newborn rabbit, the long variant w as distributed throughout the entire stroma. However, in the eyelid, althou gh the short form was present along the entire subepidermal regions both du ring fetal and neonatal development, the long form was transiently expresse d between days 21 and 24 and was restricted to the subepidermal regions at the junction of the opposing eyelids. The long form of type XII collagen wa s first detectable in the basal epithelial cells and in its basement membra ne (BM) at day 12 after birth, just before the opening of the eyelids, Ir c ontinued to be present in the corneal BM zone in the adult rabbit but was n ot present in the Limbal or conjunctival BM zone. CONCLUSIONS. The expression and distribution of the alternatively spliced f orms of type XII collagen are developmentally and differentially regulated in the cornea, the sclera, and the eyelid. Although the short form is expre ssed in the stromal matrices of the cornea and surrounding tissues from ear ly stages of corneal development, the appearance and distribution of the lo ng variant form of type XII collagen coincide with the pattern of stromal c ondensation, lts first appearance in the corneal epithelial BM precedes the eyelid opening by 1 to 2 days, possibly suggesting that it may be involved in the tighter anchoring of the corneal epithelium to the underlying tissu e or in promoting stromal condensation to assist in the separation of the c orneal epithelium from the juxtaposed palpebral conjunctival epithelium of the eyelid.