Modulation of MCT3 expression during wound healing of the retinal pigment epithelium.
OBJECTIVE
MCT3 is a proton-coupled monocarboxylate transporter preferentially expressed in the basolateral membrane of the retinal pigment epithelium (RPE) and has been shown to play an important role in regulating pH and lactate concentrations in the outer retina. Decreased expression of MCT3 in response to trauma or disease could contribute to pathologic changes in the retina. The present study followed the expression of MCT3 after wounding and re-epithelialization of chick RPE explant and human fetal (hf) RPE cultures.


METHODS
Immunofluorescence microscopy and immunoblotting were performed to determine changes in MCT expression after scratch wounding and re-epithelialization of chick RPE/choroid explant cultures and hfRPE cell monolayers.


RESULTS
MCT3 expression and basolateral polarity were maintained in chick RPE/choroid explant cultures and hfRPE monolayers. Wounding resulted in loss of MCT3 and the upregulation of MCT4 expression in migrating cells at the edge of the wound. On re-epithelialization, MCT3 was detected in chick and hfRPE cells when cells became hexagonally packed and pigmented. However, in hfRPE cells, MCT4 was consistently expressed throughout the epithelial monolayer. RPE cells at the edges of chick explants and hfRPE cultures with a free edge expressed MCT4 but not MCT3.


CONCLUSIONS
Wounding of RPE monolayers resulted in dedifferentiation of the cells at the edge of the wound, as evidenced by a loss of MCT3 and increased MCT4 expression. Collectively, these findings suggest that both cell-cell and cell-substrate interactions are essential in directing and maintaining differentiation of the RPE and expression of MCT3.
Gallagher-Colombo
Shannon
S
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Maminishkis
Arvydas
A
Tate
Susan
S
Grunwald
Gerald B
GB
Philp
Nancy J
NJ
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002829:Choroid / Q000196:embryology / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology; D055213:Retinal Pigment Epithelium / Q000196:embryology* / Q000378:metabolism; D027981:Symporters; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
D027501:Monocarboxylic Acid Transporters; C106260:SLC16A3 protein, human; D027981:Symporters