Structural Alterations in the Mouse Eye After a Targeted Heterozygous Inactivation of Type II (Pro)Collagen Gene (Col2a1)

Abstract

Abstract: : Purpose: To study the influences of targeted heterozygous inactivation of type II (pro)collagen gene (Col2a1) on eye structures in the 15–month–old C57BL/6JOlaHsd mouse. Methods: The eyes were collected from C57BL mice heterozygous for a targeted inactivation of one allele of the Col2a1 gene (Col2a1^+/– mice). The eyes of C57BL mice with normal gene alleles were used as controls (Col2a1^+/+ mice). Ocular histology was analyzed from tissue sections, stained with hematoxylin and eosin or toluidine blue. Type II collagen was localized by immunohistochemistry. Hyaluronan (HA) was stained utilizing the biotinylated complex of the hyaluronan–binding region of aggrecan and link protein (bHABC). Results: The anterior segment of the eye was well–formed in both genotypes, but structural defects were seen in the ciliary processes of the Col2a1^+/– mice. In the lens of these mice, subcapsular extracellular matrix changes were observed. Differences in retinal structures or the number of the eyes with retinal detachment were not detected between the genotypes. In Col2a1^+/– mice, staining for type II collagen was weaker in cornea, ciliary body, iris, lens, vitreous, retina, choroid and sclera than in the control mice. HA staining was detected in the extraocular tissues, ciliary body, iris and the choroid of both genotypes. HA staining was present only in the vitreous body of the control animals. In the vitreous, proteoglycan amount was decreased in the Col2a1^+/– mice. Conclusions: Heterozygous inactivation of Col2a1 gene causes structural defects in the murine eye. The observed structural changes in the ciliary body, lens and vitreous of the Col2a1^+/– mice may represent ocular features found in the human Stickler syndrome eye, where the abnormalities result from COL2A1 gene mutations which lead to functional haploinsufficiency.

Keywords: extracellular matrix • anatomy • gene/expression