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Marc Yonkers, Julia Oxford; Knockdown of Collagen 11A1 decreases zebrafish lens and optic cup diameter during early development. Invest. Ophthalmol. Vis. Sci. 2013;54(15):465.
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Collagens play essential roles in ocular structure and development as evidenced by the prevalence of specific ocular phenotypes in humans with defective collagen expression. Patients with mutations in collagen genes have defects in expression of type II or XI collagen (Stickler syndrome) and are at increased risk of retinal detachment. While retinal detachment is a common phenomenon in Stickler syndrome patients, the effects of decreased collagen synthesis on early ocular development and subsequent retinal detachment are unclear. Stickler syndrome is categorized with regards to specific collagen mutations into STL1 (COL2A1 mutation), STL2 (COL11A1 mutation), and non-ocular variant STL3 (COL11A2 mutation). Here we focus on describing the ocular phenotype in embryonic zebrafish with knockdown of collagen 11A1.
Zebrafish (Danio rerio) were bred according to published guidelines and embryos were staged according to external morphology. Antisense oligonucleotide morpholinos targeting collagen 11A1 were injected into wild-type embryos at 2-3 hours post fertilization. Embryos with uptake of the morpholino solution were raised until 72 hours post fertilization and fixed with 4% paraformaldehyde. Comparisons of ocular phenotype were made between 72 hours post fertilization wild-type and morphant zebrafish under light microscopy.
Experiments comparing optic cup and lens size show differences between wildtype (n=5) and knockdown morphants (n=5). 11A1 knockdown significantly reduced mean optic cup (WT 226 µm ± 32; 11A1 164 µm ± 29; p= 0.03) and lens diameter (WT 83 µm ± 7; 11A1 68 µm ± 9; p= 0.04).
The zebrafish animal model is widely used for developmental study and allows for knockdown of specific collagen types. These results help to define the contribution of collagen 11A1 to early eye development and yield insight into the progression of Stickler syndrome.
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