The Expression of Connexin 37, 40, 43, 45 and Pannexin 1 in the Early Human Retina and Choroid Development and Tumorigenesis

Int J Mol Sci. 2022 May 25;23(11):5918. doi: 10.3390/ijms23115918.

Abstract

The expression pattern of Connexins (Cx) 37, 40, 43, 45 and Pannexin 1 (Pnx1) was analyzed immunohistochemically, as well as semi-quantitatively and quantitatively in histological sections of developing 8th- to 12th-week human eyes and postnatal healthy eye, in retinoblastoma and different uveal melanomas. Expressions of both Cx37 and Cx43 increased during development but diminished in the postnatal period, being higher in the retina than in the choroid. Cx37 was highly expressed in the choroid of retinoblastoma, and Cx43 in epitheloid melanoma, while they were both increasingly expressed in mixoid melanoma. In contrast, mild retinal Cx40 expression during development increased to strong in postnatal period, while it was significantly higher in the choroid of mixoid melanoma. Cx45 showed significantly higher expression in the developing retina compared to other samples, while it became low postnatally and in all types of melanoma. Pnx1 was increasingly expressed in developing choroid but became lower in the postnatal eye. It was strongly expressed in epithelial and spindle melanoma, and particularly in retinoblastoma. Our results indicate importance of Cx37 and Cx40 expression in normal and pathological vascularization, and Cx43 expression in inflammatory response. Whereas Cx45 is involved in early stages of eye development, Pnx1might influence cell metabolism. Additionally, Cx43 might be a potential biomarker of tumor prognosis.

Keywords: choroid melanoma; connexin 37; connexin 40; connexin 43; connexin 45 and pannexin 1; eye development; retinoblastoma.

MeSH terms

  • Carcinogenesis / metabolism
  • Choroid / metabolism
  • Connexin 26 / metabolism
  • Connexin 43 / genetics
  • Connexin 43 / metabolism
  • Connexins / genetics
  • Connexins / metabolism
  • Gap Junction alpha-4 Protein
  • Gap Junctions / metabolism
  • Humans
  • Melanoma* / metabolism
  • Retina / metabolism
  • Retinal Neoplasms* / genetics
  • Retinal Neoplasms* / metabolism
  • Retinoblastoma* / metabolism

Substances

  • Connexin 43
  • Connexins
  • Connexin 26