Connexin43 is required for production of the aqueous humor in the murine eye.
Connexin43 is a major component of the gap junctions between pigmented and non-pigmented cells of the double-layered epithelium in the ciliary body of the eye. We directly tested the hypothesis that gap junctions play a crucial role in the production of the aqueous humor by inactivating the GJA1 (connexin43) gene in the pigmented epithelium with cre-loxP technology. To accomplish this, we crossed a line expressing cre recombinase driven by the nestin promoter and a line with floxed connexin43 alleles. Resultant lines exhibited loss of connexin43 from the pigmented epithelium, iris, retinal pigment epithelium and the lens. We observed plasma proteins in the aqueous humor and pathological changes consistent with a loss of intraocular pressure. As the ciliary body is responsible for aqueous humor production, these data support the hypothesis that the gap junctions between pigmented and non-pigmented epithelium are necessary for production of the aqueous humor that is in turn required for the generation of normal intraocular pressure and nourishment of the postnatal lens. The loss of connexin43 expression in the iris correlated with a separation of the posterior pigmented epithelium from the anterior myoepithelium and with meiosis, possibly resulting from a loss of function of the dilator pupillae.
Calera
Mónica R
MR
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Topley
Heather L
HL
Liao
Yongbo
Y
Duling
Brian R
BR
Paul
David L
DL
Goodenough
Daniel A
DA
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology / Q000378:metabolism; D018031:Connexin 43 / Q000235:genetics / Q000502:physiology*; D003315:Cornea / Q000166:cytology / Q000378:metabolism; D005123:Eye / Q000166:cytology; D005455:Fluorescent Antibody Technique; D019426:Integrases / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics; D007429:Intraocular Pressure; D007498:Iris / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012160:Retina / Q000166:cytology / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D018031:Connexin 43; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C045073:Cre recombinase; D019426:Integrases; D001616:beta-Galactosidase