title: Müller cell response to laser-induced increase in intraocular pressure in rats.
abstract: The goal of this study was to investigate the reaction of the Müller cells to elevated intraocular pressure (IOP). Elevated IOP is one of the risk factors in glaucomatous retinal ganglion cell (RGC) degeneration. Müller cells play an important role in retinal homeostasis. The reaction of Müller cells was examined by evaluating temporal changes in glutamate aspartate transporter (GLAST), glutamine synthase (GS), glial fibrillary acidic protein (GFAP), and the B-cell lymphoma (Bcl-2) using immunoblotting and immunohistochemical techniques. After IOP was elevated for 4-60 days, there was a time-related decrease in RGC ranging from 6% to 44%. There was also a time-related increase in GLAST protein reaching maximum after 3 weeks of elevated IOP. On the other hand, there was very little change in the expression of GS during the first 2 weeks followed by some increase between 21 and 60 days. An increase in Bcl-2 was biphasic with maximum increase after 4 days followed by decline after 15 and 21 days. GFAP, which is usually not expressed in normal Müller cells, was present at all time points. In all cases, the increase was most intense in the vicinity of the ganglion cells where the astrocytes and endfeet of the Müller cells are located. These results indicate that Müller cells react to the insult of elevated IOP by expressing GFAP and Bcl-2, proteins that are expressed in reactive gliosis and other pathological conditions. The increase in GLAST along with minimum change in GS indicates a disturbance in glutamate homeostasis.
authors.affiliation: Department of Biological Sciences, Allergan, Inc., Irvine, California 92612, USA. woldemussie_liz@allergan.com
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Woldemussie
authors.forename: Mercy
authors.initials: M
authors.lastname: Wijono
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Ruiz
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology / Q000528:radiation effects; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology / Q000528:radiation effects; D007429:Intraocular Pressure / Q000502:physiology* / Q000528:radiation effects; D007834:Lasers / Q000009:adverse effects*; D008297:Male; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D012160:Retina / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000473:pathology
chemical_list: D027322:Amino Acid Transport System X-AG; D005904:Glial Fibrillary Acidic Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase