Cholinergic inhibition by botulinum toxin in a rat model of congenital glaucoma raises intraocular pressure.
BACKGROUND
Cholinergic receptors are crucially involved in the regulation of intraocular pressure (IOP). Muscarinic agonists in the trabecular meshwork tissue increase aqueous humour outflow facility by a direct stimulation of ciliary muscle contraction. We investigated the contribution of cholinergic state to IOP regulation.


METHODS
Intracameral injections of botulinum toxin A (BTA) were applied in a group with four normotensive rats and a group with four glaucoma rats (genetic glaucoma model). BTA is a potent neurotoxin which inhibits presynaptic cholinergic transmission for 6-8 weeks. The same amount of saline was injected in a third group of four normotensive rats (sham condition). IOP measurements were performed preoperatively, as well as 1, 2 and 4 weeks postoperatively. Afterwards, the rat eyes were removed and subjected to immunhistochemistry and western blotting analysis using antibodies against choline acetyltransferase (CHAT).


RESULTS
Mean IOP in both normotensive groups was unaltered compared with the preoperative status. The glaucoma group showed a significant increase in the mean IOP (Student test, p<0.05) and a signal reduction for CHAT by immunolabelling in the trabecular meshwork compared with the other two groups. Western blotting confirmed the decreased expression of CHAT.


CONCLUSIONS
Our results suggest that modification of the cholinergic status in the normotensive eye does not significantly affect the IOP; cholinergic regulation of the ciliary trabecular meshwork may have differential levels of control, apart from the ciliary muscle contraction. Moreover, it seems that differential expression of the muscarinic receptors may be responsible for the decreased trabecular cholinergic state occurring in this rat model of glaucoma.
Gatzioufas
Z
Z
Department of Experimental Ophthalmology, School of Medicine, University Eye Hospital Muenster, Muenster, Germany. zisis.gatzioufas@uniklinikum-saarland.de
Charalambous
P
P
Seitz
B
B
Evers
S
S
Jonescu-Cuypers
C
C
Krause
M
M
Thanos
S
S
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western / Q000379:methods; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000032:analysis; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D003864:Depression, Chemical; D004195:Disease Models, Animal; D005260:Female; D005901:Glaucoma / Q000235:genetics* / Q000503:physiopathology; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000187:drug effects*; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D014129:Trabecular Meshwork / Q000187:drug effects / Q000201:enzymology
D015415:Biomarkers; D018680:Cholinergic Antagonists; D002795:Choline O-Acetyltransferase; D019274:Botulinum Toxins, Type A