Limiting the proliferation and reactivity of retinal Müller cells during experimental retinal detachment: the value of oxygen supplementation.
OBJECTIVE
To assess the role of hypoxia in inducing the proliferation, hypertrophy, and dysfunction of Muller cells in detached retina and the effectiveness of supplemental oxygen in limiting these reactions.


METHODS
Retinal detachments were produced in the right eye of each of 13 cats; the cats survived surgery for 3 days, during which six were kept in normoxia (room air, 21%) and seven in hyperoxia (70% oxygen). Retinas were labeled for proliferation with an antibody (MIB-1) to a cell cycle protein (Ki-67), for evidence of hypertrophy employing antibodies to the intermediate filament protein glial fibrillary acidic protein (GFAP) and to beta-tubulin and for disturbance of glutamate neurochemistry employing antibodies to glutamate to a glutamate receptor (GluR-2) and to glutamine synthetase.


RESULTS
Results from the two animals kept in normoxia after retinal detachment confirmed previous reports that detachment caused the proliferation of Muller cells, the hypertrophy of Muller cell processes, and the disruption of glutamate recycling by Muller cells. Oxygen supplementation during detachment reduced Muller cell proliferation and hypertrophy and reduced the abnormalities in the distributions of glutamate, GluR-2, and glutamine synthetase.


CONCLUSIONS
Oxygen supplementation reduced the reaction of retinal Muller cells to retinal detachment, limiting their proliferation and helping to maintain their normal structure and function. In the clinical setting, oxygen supplementation between diagnosis and reattachment surgery may reduce the incidence and severity of glial-based complications, such as proliferative vitreoretinopathy.
Lewis
G
G
Neuroscience Research Institute, Santa Barbara, California, USA.
Mervin
K
K
Valter
K
K
Maslim
J
J
Kappel
P J
PJ
Stone
J
J
Fisher
S
S
D000818:Animals; D034961:Antigens, Nuclear; D015415:Biomarkers; D002415:Cats; D002453:Cell Cycle / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000276:immunology / Q000378:metabolism; D018698:Glutamic Acid / Q000276:immunology / Q000378:metabolism; D006984:Hypertrophy; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D010102:Oxygen Inhalation Therapy; D018091:Receptors, AMPA / Q000276:immunology / Q000378:metabolism; D012163:Retinal Detachment / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome; D014404:Tubulin / Q000276:immunology / Q000378:metabolism
D034961:Antigens, Nuclear; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018091:Receptors, AMPA; D014404:Tubulin; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase; C104722:glutamate receptor ionotropic, AMPA 2