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Tara L. Favazza, Anne B. Fulton, Ronald M. Hansen, James D. Akula; Effect Of A Carbonic Anhydrase Inhibitor (Dorzolamide)On Retinal Function Depends On Age. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6067.
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Carbonic anhydrases (CAs) assist in many functions, including cell respiration and transportation of CO2, electrolyte secretion, calcification, etc. In the eye, CA inhibitors (CAIs) change retinal ion concentrations and effect circulation and intraocular pressure. CAIs also alter electroretinographic (ERG) responses, but the effect of CAIs on the immature retina is unknown. This study examined the direction, magnitude, and timecourse of the effect of a single application of the CAI dorzolamide (DZM; Trusopt, Merck) on retinal function in infant, adolescent, and adult rats.
Dark-adapted Sprague Dawley rats (N=13) were tested at three ages, postnatal day (P) 21±1, P33, and P70±6. In anesthetized subjects, cycloplegia was induced with a combination of phenylephrine and cyclopentolate hydrochlorides. Body temperature was maintained with a warming plate. Gold electrodes were placed on each eye, the reference was placed in the mouth, and the ground was affixed to the tail. Two drops of DZM were instilled in one eye, and saline in the other. ERGs were evoked with a flash producing ~10,000 rhodopsin photoisomerizations every 3 minutes for 99 minutes. The amplitude and implicit time of the a- and b-wave were recorded and expressed as a percent change from the response observed immediately after drop administration. The timecourse of a- and b-wave changes were captured by the KM parameter of each subject’s data fitted to the Michaelis-Menten model. Changes in amplitude and implicit time were evaluated by four-factor (eye×age×wavelet×time) ANOVA; kinetics was also analyzed by ANOVA (age×wavelet).
Overall, a significant increase in a- and b-wave response amplitudes was found in DZM treated eyes (PEYE=0.017). A- and b-wave responses grew larger with time (PTIME<0.001) with nearly identical courses (PWAVELET=0.18). The effect of DZM grew with age (~120% at P21, ~175% at P33, ~220% at P70; PAGE=0.034). The small change at P21 did not allow for a determination of kinetics, but KM was slower at P70 than P33 (PAGE=0.038). Neither a- nor b-wave implicit time was altered at any age.
DZM increases ERG response amplitudes. This DZM effect increases with maturation. Developmental changes in the retinal ionic milieu and circulation may be responsible for the increase with age. Further studies are needed to determine the underlying mechanism of DZM action on retinal neurons.
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