Inhibition of membrane-bound carbonic anhydrase enhances subretinal fluid absorption and retinal adhesiveness.
BACKGROUND
The clinical use of currently available carbonic anhydrase (CA) inhibitors is limited by systemic side-effects, thought to result from the inhibition of intracellular CA isoenzymes. This study investigates how benzolamide, a carbonic anhydrase inhibitor which does not readily penetrate cell membranes, modulates retinal pigment epithelium functions relative to acetazolamide, which diffuses into the cytosol.


METHODS
Small retinal detachments were made in Dutch rabbits by injecting saline into the subretinal space. Detachment height was measured using a dual He-Ne beam YAG laser focusing system, and the fluid absorption rate was calculated before and after intravenous injections of saline, acetazolamide or benzolamide. Retinal adhesiveness was determined by peeling the retina from the RPE and measuring the amount of adherent pigment.


RESULTS
The baseline fluid absorption rate of 0.04 microl/mm(2)/h was unchanged after injection of 0.9% NaCl or low-dose benzolamide (5 mg/kg). The absorption increased to about 0.14 microl/mm(2)/h after higher benzolamide doses (20-40 mg/kg) and to 0.13 microl/mm(2)/h after acetazolamide (20 mg/kg). Both acetazolamide and benzolamide significantly slowed the post-enucleation failure of retinal adhesiveness.


CONCLUSIONS
Since benzolamide had effects similar to acetazolamide, inhibition of membrane-bound CA appears to be sufficient to enhance subretinal fluid absorption and retinal adhesiveness. Membrane-specific CA inhibitors may therefore be of clinical value if they minimize side-effects from intracellular CA inhibition.
Wolfensberger
T J
TJ
Department of Ophthalmology, Stanford University School of Medicine, Stanford, USA.
Chiang
R K
RK
Takeuchi
A
A
Marmor
M F
MF
D000042:Absorption / Q000187:drug effects; D000086:Acetazolamide / Q000494:pharmacology*; D000268:Adhesiveness / Q000187:drug effects; D000818:Animals; D001574:Benzolamide / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism*; D007424:Intracellular Fluid / Q000201:enzymology; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D012163:Retinal Detachment / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D001574:Benzolamide; D000086:Acetazolamide