Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 20, Pages 8514-8519Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0702899104
Keywords
choriocapillaris; CO2/bicarbonate transport; Muller cell; pH regulation; photoreceptor
Categories
Funding
- NEI NIH HHS [EY08922, P30 EY002687, R03 EY015113, R01 EY008922, EY015113, EY02687] Funding Source: Medline
- NIDCD NIH HHS [P30 DC004665] Funding Source: Medline
- NIDDK NIH HHS [DK40163, R01 DK040163, R01 DK040163-19] Funding Source: Medline
- NIGMS NIH HHS [R01 GM034182-22, GM34182, R01 GM034182] Funding Source: Medline
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Members of the carbonic anhydrase (CA) family play an important role in the regulation of pH, CO2, ion, and water transport. CA IV and CA XIV are membrane-bound isozymes expressed in the eye. CA IV immunostaining is limited to the choriocapillaris overlying the retina, whereas CA XIV is expressed within the retina in Muller glial cells and retinal pigment epithelium. Here, we have characterized the physiological and morphological phenotype of the CA IV-null, CA XIV-null, and CA IV/CA XIV-double-null mouse retinas. Flash electroretinograms performed at 2, 7, and 10 months of age showed that the rod/cone a-wave, b-wave, and cone b-wave were significantly reduced (26-45%) in the CA XIV-null mice compared with wild-type littermates. Reductions in the dark-adapted response were not progressive between 2 and 10 months, and no differences in retinal morphology were observed between wildtype and CA XIV-null mice. Muller cells and rod bipolar cells had a normal appearance. Retinas of CA IV-null mice showed no functional or morphological differences compared with normal littermates. However, CA IV/CA XIV double mutants showed a greater deficit in light response than the CA XIV-null retina. Our results indicate that CA XIV, which regulates extracellular pH and pCO(2), plays an important part in producing a normal retinal light response. A larger functional deficit in the CA IV/CA XIV double mutants suggests that CA IV can also contribute to pH regulation, at least in the absence of CA XIV.
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