Sostdc1 is expressed in all major compartments of developing and adult mammalian eyes

Graefes Arch Clin Exp Ophthalmol. 2019 Nov;257(11):2401-2427. doi: 10.1007/s00417-019-04462-4. Epub 2019 Sep 16.

Abstract

Purpose: This study was conducted in order to study Sostdc1 expression in rat and human developing and adult eyes.

Methods: Using the yeast signal sequence trap screening method, we identified the Sostdc1 cDNA encoding a protein secreted by the adult rat retinal pigment epithelium. We determined by in situ hybridization, RT-PCR, immunohistochemistry, and western blot analysis Sostdc1 gene and protein expression in developing and postnatal rat ocular tissue sections. We also investigated Sostdc1 immunohistolocalization in developing and adult human ocular tissues.

Results: We demonstrated a prominent Sostdc1 gene expression in the developing rat central nervous system (CNS) and eyes at early developmental stages from E10.5 days postconception (dpc) to E13 dpc. Specific Sostdc1 immunostaining was also detected in most adult cells of rat ocular tissue sections. We also identified the rat ocular embryonic compartments characterized by a specific Sostdc1 immunohistostaining and specific Pax6, Sox2, Otx2, and Vsx2 immunohistostaining from embryonic stages E10.5 to E13 dpc. Furthermore, we determined the localization of SOSTDC1 immunoreactivity in ocular tissue sections of developing and adult human eyes. Indeed, we detected SOSTDC1 immunostaining in developing and adult human retinal pigment epithelium (RPE) and neural retina (NR) as well as in several developing and adult human ocular compartments, including the walls of choroidal and scleral vessels. Of utmost importance, we observed a strong SOSTDC1 expression in a pathological ocular specimen of type 2 Peters' anomaly complicated by retinal neovascularization as well in the walls ofother pathological extra-ocular vessels. CONCLUSION: As rat Sostdc1 and human SOSTDC1 are dual antagonists of the Wnt/β-catenin and BMP signaling pathways, these results underscore the potential crucial roles of these pathways and their antagonists, such as Sostdc1 and SOSTDC1, in developing and adult mammalian normal eyes as well as in syndromic and nonsyndromic congenital eye diseases.

Keywords: BMP; Eye development; Sostdc1; Type 2 Peters' anomaly; Wnt/β-catenin.

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics*
  • Aged
  • Animals
  • Blotting, Western
  • Child, Preschool
  • Disease Models, Animal
  • Eye Diseases, Hereditary / genetics*
  • Eye Diseases, Hereditary / metabolism
  • Female
  • Gene Expression Regulation, Developmental*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • RNA / genetics*
  • Rats
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / growth & development
  • Retinal Pigment Epithelium / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • SOSTDC1 protein, human
  • RNA