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

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.

The Role of Connexin 43 in Renal Disease: Insights from In Vivo Models of Experimental Nephropathy

“…Indeed, a high expression of this Cx has been found in a diseased human eye (diabetic retinopathy, epithelioid and mixoid melanoma, etc. ), playing a role in the establishment of the inflammatory process and the proliferation of tumor cells [ 28 ].…”

A metastasis-associated Pannexin1 mutant (Panx11-89) forms a minimalist ATP release channel

“…Extracellular ATP and its catabolites generated by ecto-ATPases are critical players in cancer biology 1 2 3 4 5 . Thus, as an ATP release channel, Pannexin1 (Panx1) has thus gained considerable attention as a mediator of metastasis [6][7][8][9][10][11][12][13] . Based on the direct correlation of expression of a truncated form of Panx1 channel (Panx1 ) with metastatic potential of breast cancer cells, a mechanism for metastatic cell survival in the microvasculature has been proposed 14 .…”

Expression of Cell Cycle Markers and Proliferation Factors during Human Eye Embryogenesis and Tumorigenesis

“…During embryogenesis, the timing of cell fate determination regulates the different cell types, which is thought to be controlled by a tightly coordinated regulatory program of proliferation, cell cycle termination, and differentiation [ 1 ]. Because of the close relationship between developmental plasticity of the eye and tumorigenesis, these regulatory programs might be reactivated during ocular carcinogenesis [ 2 ]. However, the understanding of this complex gene regulatory network and the mechanisms underlying ocular carcinogenesis has not been fully elucidated [ 3 ].…”