Pupillographic evaluation of the time course of atropine effects in the mouse eye.
OBJECTIVE
The nonselective muscarinic antagonist atropine is currently the most potent drug against myopia development in both humans and animal models. However, the mechanism by which myopia is suppressed is still unknown, and the time course of its action is not well documented. Therefore, we have studied the duration of mydriasis in the mouse, a new model of myopia, after topical application of a single eye drop with different doses of atropine.


METHODS
The light-induced pupil response of the C57BL/6 (B6) wildtype strain was studied in alert mice that were restrained by grasping their necks. A video image-processing program detected the pupil and measured its diameter at 25 Hz sampling rate. To stimulate, an arrangement of green LEDs, which was attached to the recording video camera, could be flashed for 40 ms by pressing a key on the keyboard. A single drop of atropine solution (1, 0.5, or 0.1%) was instilled in one eye and the recovery of the pupil responses was followed for at least 150 h. Both eyes were measured.


RESULTS
1) Under the defined stimulation conditions, untreated wildtype mice displayed a pupil constriction of 23.7 +/- 2.4%. 2) All doses of atropine caused complete suppression of the pupil responses in the treated eyes within 1 min. 3) The pupil responses of the fellow eyes remained unaffected and were not different from those in untreated animals. 4) The recovery from mydriasis was very slow and did not show clear differences with dose. The extrapolated duration of complete recovery was about 10 d (0.1%: 217 h; 0.5%: 230 h; 1%: 294 h).


CONCLUSIONS
Atropine caused a longlasting suppression of the pupil responses in the mouse eye. That the duration of recovery was not obviously dose-dependent suggests that all doses used in this study were saturating the receptors in the iris musculature.
Schaeffel
Frank
F
University Eye Hospital, Section for Neurobiology of the Eye, 72076 Tuebingen, Germany. frank.schaeffel@uni-tuebingen.de
Burkhardt
Eva
E
D000818:Animals; D001285:Atropine / Q000008:administration & dosage*; D003941:Diagnostic Techniques, Ophthalmological; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007498:Iris / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D015878:Mydriasis / Q000139:chemically induced / Q000503:physiopathology; D009216:Myopia / Q000188:drug therapy / Q000503:physiopathology*; D009883:Ophthalmic Solutions; D010775:Photic Stimulation; D011680:Pupil / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014741:Video Recording
D018727:Muscarinic Antagonists; D009883:Ophthalmic Solutions; D001285:Atropine