Connexin-mediated communication controls cell proliferation and is essential in retinal histogenesis.
Connexin (Cx) channels and hemichannels are involved in essential processes during nervous system development such as apoptosis, propagation of spontaneous activity and interkinetic nuclear movement. In the first part of this study, we extensively characterized Cx gene and protein expression during retinal histogenesis. We observed distinct spatio-temporal patterns among studied Cx and an overriding, ubiquitous presence of Cx45 in progenitor cells. The role of Cx-mediated communication was assessed by using broad-spectrum (carbenoxolone, CBX) and Cx36/Cx50 channel-specific (quinine) blockers. In vivo application of CBX, but not quinine, caused remarkable reduction in retinal thickness, suggesting changes in cell proliferation/apoptosis ratio. Indeed, we observed a decreased number of mitotic cells in CBX-injected retinas, with no significant changes in the expression of PCNA, a marker for cells in proliferative state. Taken together, our results pointed a pivotal role of Cx45 in the developing retina. Moreover, this study revealed that Cx-mediated communication is essential in retinal histogenesis, particularly in the control of cell proliferation.
Kihara
Alexandre H
AH
Núcleo de Cognição e Sistemas Complexos, Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, Santo André, SP, Brazil. alexandrekihara@gmail.com
Santos
Taisa O
TO
Osuna-Melo
Edgard J
EJ
Paschon
Vera
V
Vidal
Kallene S M
KS
Akamine
Priscilla S
PS
Castro
Leandro M
LM
Resende
Rodrigo R
RR
Hamassaki
Dânia E
DE
Britto
Luiz R G
LR
D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002491:Central Nervous System Agents / Q000494:pharmacology; D017630:Connexins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D051248:Retinal Horizontal Cells / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D002491:Central Nervous System Agents; D017630:Connexins; D018809:Proliferating Cell Nuclear Antigen; D011803:Quinine; D002229:Carbenoxolone