| First Author | Aikio M | Year | 2013 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 54 |
| Issue | 12 | Pages | 7450-62 |
| PubMed ID | 24135756 | Mgi Jnum | J:215140 |
| Mgi Id | MGI:5604701 | Doi | 10.1167/iovs.13-13039 |
| Citation | Aikio M, et al. (2013) Collagen XVIII short isoform is critical for retinal vascularization, and overexpression of the Tsp-1 domain affects eye growth and cataract formation. Invest Ophthalmol Vis Sci 54(12):7450-62 |
| abstractText | PURPOSE: Collagen XVIII deficiency leads to anterior and posterior eye defects in Col18a1(-/-) mice, and overexpression of its C-terminal endostatin domain under a K14 promoter leads to cataract. We studied the consequences of K14-driven overexpression of the thrombospondin-1 (Tsp-1)-like domain, and also the roles of the three collagen XVIII isoforms in mice specifically lacking either the promoter 1-derived short or the promoter 2-derived medium/long isoforms. METHODS: Two transgenic lines were generated and compared to Col18a1(-/-) and promoter 1 and 2 knockouts. Enucleated eyes were analyzed histopathologically, immunohistochemically, biochemically, and ultrastructurally. IOP was measured by noninvasive tonometry, and the anterior chamber was studied in vivo using a slit-lamp and optical coherence tomography. RESULTS: Overexpression of the Tsp-1 transgene in an FVB/N background resulted in increased axial length, and substantial incidences of cataract, lens subluxation, phthisis, retinal ablation, corneal vascularization, and intraocular hemorrhages. The FVB/N Col18a1(-/-) mice were affected similarly. The findings in the knockout and transgenic lines were milder in a C57BL/6JOlaHsd (B6) background. Studies with the promoter-specific knockouts revealed the short isoform as the sole variant in the lens capsule and inner limiting membrane, while the ciliary body, iris, and Bruch's membrane contained short and medium/long isoforms. Lack of the short isoform, but not of the medium/long isoforms, caused aberrant retinal vascularization. CONCLUSIONS: An excess of the collagen XVIII Tsp-1 domain is deleterious in the eye, possibly by impairing certain functions of the full-length molecule. Moreover, the short isoform is the critical variant in the development of the posterior eye structures. |
