| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the Department of Biological Sciences, Allergan Inc., Irvine, California.
PURPOSE. To examine the neuroprotective effect of the
2-adrenergic agonist brimonidine in a chronic ocular
hypertension model.
METHODS. Intraocular pressure (IOP) was elevated by laser photocoagulation of episcleral and limbal veins. Retinal ganglion cell loss was evaluated in wholemounted retinas. Brimonidine or timolol was administered, either at the time of or 10 days after IOP elevation and continued for 3 weeks. Drug-related immunohistochemical changes in glial fibrillary acidic protein (GFAP) were also determined after 3 weeks.
RESULTS. Laser treatment caused a twofold IOP increase over baseline that was maintained for 2 months. A time-dependent loss of ganglion cells occurred with elevated IOP. Systemic administration of brimonidine or timolol caused little decrease in IOP. After 3 weeks of elevated IOP, ganglion cell loss in control rats was 33% ± 3%. Brimonidine reduced the progressive loss of ganglion cells to 26% ± 1% and 15% ± 2% at doses of 0.5 and 1 mg/kg · d, respectively. Timolol had no effect. Ten days of high IOP resulted in 22% ± 4% ganglion cell loss. Brimonidine administration initiated 10 days after IOP elevation prevented any further loss of ganglion cells. In vehicle- or timolol-treated rats, ganglion cell loss continued to 33%. The increase in immunoreactivity of GFAP in ocular hypertensive retinas was attenuated by brimonidine.
CONCLUSIONS. Systemic application of brimonidine or timolol had little effect on IOP. Brimonidine, but not timolol, showed significant protection of retinal ganglion cells when applied at the time of IOP elevation and prevented further cell loss when applied after IOP was elevated. This indicates that brimonidine has a neuroprotective activity unrelated to its effect on ocular hypotension.
This article has been cited by other articles:
|
|
 |
|
  C.-J. Dong, Y. Guo, P. Agey, L. Wheeler, and W. A. Hare {alpha}2 Adrenergic Modulation of NMDA Receptor Function as a Major Mechanism of RGC Protection in Experimental Glaucoma and Retinal Excitotoxicity Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4515 - 4522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q.-L. Fu, B. Hu, W. Wu, R. B. Pepinsky, S. Mi, and K.-F. So Blocking LINGO-1 Function Promotes Retinal Ganglion Cell Survival Following Ocular Hypertension and Optic Nerve Transection Invest. Ophthalmol. Vis. Sci., March 1, 2008; 49(3): 975 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kusari, S. Zhou, E. Padillo, K. G. Clarke, and D. W. Gil Effect of Memantine on Neuroretinal Function and Retinal Vascular Changes of Streptozotocin-Induced Diabetic Rats Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5152 - 5159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bakalash, A. Rolls, O. Lider, and M. Schwartz Chondroitin Sulfate-Derived Disaccharide Protects Retinal Cells from Elevated Intraocular Pressure in Aged and Immunocompromised Rats Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1181 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-J. Dong, Y. Guo, L. Wheeler, and W. A. Hare {alpha}2 Adrenergic Receptor-Mediated Modulation of Cytosolic Ca++ Signals at the Inner Plexiform Layer of the Rat Retina Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1410 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A T Fung, S E Reid, M P Jones, P R Healey, P J McCluskey, and J C Craig Meta-analysis of randomised controlled trials comparing latanoprost with brimonidine in the treatment of open-angle glaucoma, ocular hypertension or normal-tension glaucoma Br. J. Ophthalmol., January 1, 2007; 91(1): 62 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. P. Sullivan, E. WoldeMussie, L. Macnab, G. Ruiz, and D. V. Pow Evoked Expression of the Glutamate Transporter GLT-1c in Retinal Ganglion Cells in Human Glaucoma and in a Rat Model. Invest. Ophthalmol. Vis. Sci., September 1, 2006; 47(9): 3853 - 3859. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Li, B.-Y. Chen, D. K. Tay, H. H. L. Chan, M.-L. Pu, and K.-F. So Melanopsin-expressing retinal ganglion cells are more injury-resistant in a chronic ocular hypertension model. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 2951 - 2958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-H. Wang, J. C. Millar, I.-H. Pang, M. B. Wax, and A. F. Clark Noninvasive Measurement of Rodent Intraocular Pressure with a Rebound Tonometer Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4617 - 4621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mayor-Torroglosa, P. De la Villa, M. E. Rodriguez, M. P. L. Lopez-Herrera, M. Aviles-Trigueros, A. Garcia-Aviles, J. Miralles de Imperial, M. P. Villegas-Perez, and M. Vidal-Sanz Ischemia Results 3 Months Later in Altered ERG, Degeneration of Inner Layers, and Deafferented Tectum: Neuroprotection with Brimonidine Invest. Ophthalmol. Vis. Sci., October 1, 2005; 46(10): 3825 - 3835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F B Kalapesi, M T Coroneo, and M A Hill Human ganglion cells express the alpha-2 adrenergic receptor: relevance to neuroprotection Br. J. Ophthalmol., June 1, 2005; 89(6): 758 - 763. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Guo, S. E. Moss, R. A. Alexander, R. R. Ali, F. W. Fitzke, and M. F. Cordeiro Retinal Ganglion Cell Apoptosis in Glaucoma Is Related to Intraocular Pressure and IOP-Induced Effects on Extracellular Matrix Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 175 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. V. Bui, B. Edmunds, G. A. Cioffi, and B. Fortune The Gradient of Retinal Functional Changes during Acute Intraocular Pressure Elevation Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 202 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Cordeiro, L. Guo, V. Luong, G. Harding, W. Wang, H. E. Jones, S. E. Moss, A. M. Sillito, and F. W. Fitzke Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration PNAS, September 7, 2004; 101(36): 13352 - 13356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. C. Chauhan, T. L. LeVatte, C. A. Jollimore, P. K. Yu, H. A. Reitsamer, M. E. M. Kelly, D.-Y. Yu, F. Tremblay, and M. L. Archibald Model of Endothelin-1-Induced Chronic Optic Neuropathy in Rat Invest. Ophthalmol. Vis. Sci., January 1, 2004; 45(1): 144 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T Aung, F T S Oen, H-T Wong, Y-H Chan, B-K Khoo, Y-P Liu, C-L Ho, J See, L H Thean, A C Viswanathan, et al. Randomised controlled trial comparing the effect of brimonidine and timolol on visual field loss after acute primary angle closure Br. J. Ophthalmol., January 1, 2004; 88(1): 88 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D W Evans, S L Hosking, D Gherghel, and J D Bartlett Contrast sensitivity improves after brimonidine therapy in primary open angle glaucoma: a case for neuroprotection Br. J. Ophthalmol., December 1, 2003; 87(12): 1463 - 1465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H E Fazzone, M J Kupersmith, and J Leibmann Does topical brimonidine tartrate help NAION? Br. J. Ophthalmol., September 1, 2003; 87(9): 1193 - 1194. [Full Text] [PDF]
|
|
|
|
|
|
B. C. Chauhan, J. Pan, M. L. Archibald, T. L. LeVatte, M. E. M. Kelly, and F. Tremblay Effect of Intraocular Pressure on Optic Disc Topography, Electroretinography, and Axonal Loss in a Chronic Pressure-Induced Rat Model of Optic Nerve Damage Invest. Ophthalmol. Vis. Sci., September 1, 2002; 43(9): 2969 - 2976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Baptiste, A. T. E. Hartwick, C. A. B. Jollimore, W. H. Baldridge, B. C. Chauhan, F. Tremblay, and M. E. M. Kelly Comparison of the Neuroprotective Effects of Adrenoceptor Drugs in Retinal Cell Culture and Intact Retina Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2666 - 2676. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
