Altered calcium signaling in an experimental model of glaucoma.
OBJECTIVE
To investigate calcium signaling in a rat experimental model of glaucoma.


METHODS
A method for labeling ganglion cell layer (GCL) neurons with the calcium indicator Fura-2 in flat-mounted retinas of adult rats was established. Pharmacologically evoked responses in laser-induced glaucomatous and control retinas were imaged 2 weeks after the initial laser treatment. The optic nerves of the same eyes were evaluated for neurodegenerative changes.


RESULTS
After laser treatment, intraocular pressure (IOP) was elevated 1.5- to 4.9-fold (24.70 ± 15.57 mm Hg) compared with control eyes (8.71 ± 1.53 mm Hg), and the area of neurodegenerative axons in optic nerve sections of laser-treated eyes was increased by 1.2- to 13.3-fold. The basal intracellular Ca(2+) level, as revealed by the Fura-2 ratio, was elevated in GCL neurons of laser-treated eyes compared with controls. This might suggest a mild degree of damage at the level of the soma in the GCL neurons of eyes with elevated IOP. Although glaucomatous GCL neurons remained functional as assessed pharmacologically, analysis of imaging data revealed that responses evoked by a brief application of ATP were slightly reduced rather than increased in the cells of laser-treated eyes compared with controls. No significant relationships were found between IOP/optic nerve damage and functional characteristics (basal intracellular Ca(2+) level or response to carbachol/elevated K(+)/ATP) within cells of laser-treated eyes.


CONCLUSIONS
Ca(2+) imaging is a useful tool to map altered physiological characteristics of individual GCL neurons in the glaucomatous eye.
Niittykoski
Minna
M
Department of Ophthalmology, University of Kuopio, Kuopio, Finland. mijoni@gmail.com
Kalesnykas
Giedrius
G
Larsson
Kim P
KP
Kaarniranta
Kai
K
Akerman
Karl E O
KE
Uusitalo
Hannu
H
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004195:Disease Models, Animal; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology; D007429:Intraocular Pressure; D008297:Male; D009901:Optic Nerve Diseases / Q000378:metabolism* / Q000473:pathology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D018679:Cholinergic Agonists; C049925:fura-2-am; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D002217:Carbachol; D002118:Calcium; D016257:Fura-2