Glial cell reactivity in a porcine model of retinal detachment.
OBJECTIVE
Detachment of the neural retina from the pigment epithelium causes, in addition to photoreceptor deconstruction and neuronal cell remodeling, an activation of glial cells. It has been suggested that gliosis contributes to the impaired recovery of vision after reattachment surgery that may involve both formerly detached and nondetached retinal areas. Müller and microglial cell reactivity was monitored in a porcine model of rhegmatogenous retinal detachment, to determine whether gliosis is present in detached and nondetached retinal areas.


METHODS
Local detachment was created in the eyes of adult pigs by subretinal application of hyaluronate. Retinal slices were immunostained against glial intermediate filaments and K+ and water channel proteins (aquaporin-4, Kir4.1, Kir2.1), and P2Y receptor proteins. In retinal wholemounts, adenosine 5'-triphosphate (ATP)-induced intracellular Ca2+ responses of Müller cells were recorded, and microglial and immune cells were labeled with Griffonia simplicifolia agglutinin isolectin I-B4. K+ currents were recorded from isolated Müller cells.


RESULTS
At 3 and 7 days after surgery, Müller cells in detached retinas showed a pronounced gliosis, as revealed by the increased expression of the intermediate filaments glial fibrillary acidic protein and vimentin, by the decrease of Kir4.1 immunoreactivity and of the whole-cell K+ currents, and by the increased incidence of cells that showed Ca2+ responses on stimulation of purinergic (P)2 receptors by ATP. By contrast, the immunohistochemical expression of Kir2.1 and aquaporin-4 were not altered after detachment. The increase in the expression of intermediate filaments, the decrease of the whole-cell K+ currents and of the Kir4.1 immunolabeling, and the increase in the Ca2+ responsiveness of Müller cells were also observed in attached retinal areas surrounding the focal detachment. The density of microglial-immune cells at the inner surface of the retinas increased in both detached and nondetached retinal areas. The immunoreactivities for P2Y1 and P2Y2 receptor proteins apparently increased only in detached areas.


CONCLUSIONS
Reactive responses of Müller and microglial cells are not restricted to detached retinal areas but are also observed in nondetached regions of the porcine retina. The gliosis in the nondetached retina may reflect, or may contribute to, neuronal degeneration that may explain the impaired recovery of vision observed in human subjects after retinal reattachment surgery.
Iandiev
Ianors
I
Paul Flechsig Institute of Brain Research, Leipzig, Germany.
Uckermann
Ortrud
O
Pannicke
Thomas
T
Wurm
Antje
A
Tenckhoff
Solveig
S
Pietsch
Uta-Carolin
UC
Reichenbach
Andreas
A
Wiedemann
Peter
P
Bringmann
Andreas
A
Uhlmann
Susann
S
D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D012163:Retinal Detachment / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D000098854:Kcnj10 Channel
D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D000098854:Kcnj10 Channel; C489461:Kir2.1 channel; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D018048:Receptors, Purinergic P2; D002118:Calcium