Table 2.
Animals models of ECM component mutations demonstrate roles of the ILM in retinal development
| Gene | Protein name | Mutation description | Species | Phenotype | Reference |
|---|---|---|---|---|---|
| Col4A1 | Type IV collagen, alpha 1 subunit | Autosomal dominant mutation; disrupted splice acceptor site, causing deletion of 17 amino acids in the collagen triple helical domain resulting in improper protein folding | Mouse | ocular dysgenesis, neuronal localization defects | Labelle-Dumais et al., 2011 |
| Col18A1 | Type XVIII collagen, alpha 1 subunit | Homozygous knock-out | Mouse | abnormal outgrowth of retinal vessels; reduced expression of VEGF in retinas; increased retinal astrocytes; lack of vitreous fibril insertion into the ILM |
Fukai, 2002; Hurskainen et al., 2005 |
| ItgaA6 | Integrin, alpha 6 subunit | Homozygous knock-out | Mouse | disorganized basement membrane; ectopic neuroblasts in vitreous | Georges-Labouesse et al., 1998 |
| ISPDL79* | Isoprenoid synthase domain-containing protein | Autosomal recessive; lack mature glycan chains for dystroglycan to bind laminin | Mouse | ILM disruption and, defective axon guidance for RGCs; pups die at P0 due to respiratory failure |
Clements et al., 2017; Wright et al., 2012 |
| Lama1 (bala69) | Laminin, alpha 1 subunit | Dominant-negative mutation; missense mutation affecting disulfide bridge formation | Zebrafish | RGC axonal projection defect; ectopic photoreceptors in inner retina; hyaloid vessels lack capillaries | Semina et al., 2006 |
| Lama1nmf223 | Autosomal recessive point mutation; amino acid substitution at receptor binding and polymerization sites | Mouse | Normal appearing ILM; astrocytes and vasculature migrate ectopically into vitreous; astrocytes persist and proliferate in vitreous, forming dense mesh resembling epiretinal membranes | Edwards et al., 2011 | |
| Lama1tm1.Olf | Conditional knock-out driven by CMV-Cre, bypasses embryonic lethality | Mouse | Very thin ILM; Müller cell processes extend into vitreous through frequent breaks in ILM Similar vascular patterns as those found in Lama1nmf223 |
Alpy et al., 2005; Edwards et al., 2011 |
|
| Lama4 | Laminin, alpha 4 subunit | Homozygous knock-out | Mouse | retinal hemorrhage due to endothelial BM defect; increased vessel branching, reduced vascular maturation, reduced lumen size |
Stenzel et al., 2011; Thyboll et al., 2002 |
| Lamb2 | Laminin, beta 2 subunit | Homozygous nonsense mutation created by inserting stop codons into exon 3; no full length protein produced | Mouse Human |
Mice: abnormal rod photoreceptor synapse formation; abnormal electroretinograms Humans: Pierson syndrome; ocular defects include microcorcia, glaucoma, cataracts, retinal detachment |
Libby et al., 1999
Zenker et al., 2004 |
| Lamc3 | Laminin, gamma 3 subunit | Homozygous knock-out created by vector targeted exon 1 deletion | Mouse | altered vasculature, increased branching in OPL | Li et al., 2012 |
| Lamb2 / Lamc3 | Laminin, beta 2 & Laminin, gamma 3 | Homozygous compound knock-out | Mouse | Müller cells and RGC processes extend into vitreous; thickened Bruch’s membrane; disorganized PR outer segment; synaptic defects | Pinzón-Duarte et al., 2010 |
| Largemyd | Xylosyl- And Glucuronyltransferase 1 | Autosomal recessive allele; intragenic deletion of the glycosyltransferase gene Large | Mouse | disrupted ILM, ectopic cells in vitreous; hypoglycosylation of dystroglycan; retinal vessel tortuosity and leakage | Lee et al., 2005 |
| α-Cre;Ugdhflox | UDP-Glucose 6-dehydrogenase | Connditional knock-out of the GAG synthesis gene Ugdh under the control of the retinaspecific regulatory element alpha of murine Pax6 | Mouse | large ILM defect in peripheral retina; failed astrocyte migration to defective areas |
Marquardt et al., 2001; Tao and Zhang, 2016 |