Abstract
Abstract: :
Purpose: Carbonic anhydrases (CAs) are zinc–containing enzymes that catalyze the reversible hydration of carbon dioxide (H2O + CO2 ↔ HCO3– + H+). This simple chemical reaction has important implications for pH homeostasis, carbon dioxide and ion transport, respiration, and many other critical processes in living systems. The CA family includes 15 different isozymes that are distributed in a tissue–specific fashion. CA XIV, a membrane bound isozyme, is highly expressed in neural retina and RPE, particularly in Muller glial cells. Here we characterize the pathological and physiological phenotype of the CA XIV null mutant mouse retina. Methods: We created CA XIV null mutant mice. Flash electroretinograms (ERG’s) were performed at 2, 7, and 10 months of age. After testing, eyecups were harvested, fixed, and then processed and embedded in plastic for pathology or frozen for immunohistochemistry (IHC). Antibodies against glial fibrillary acidic protein (GFAP) and protein kinase C (PKC) were used to label Muller glial and rod bipolar cells, respectively. Results: CA XIV mice were healthy overall with no gross phenotypic deficiencies. The rod/cone a–wave, b–wave, and cone b–wave were significantly reduced (26 – 45%) in the CA XIV null mice compared to wild type littermates. Interestingly, these reductions in light response were unchanged over time between 2 and 10 months. No differences in gross retinal pathology were observed between wild type and CA XIV null mice. Muller glial cells and rod bipolar cells had a normal appearance in CA XIV null mice compared to wild type littermates, as indicated by GFAP and PKC labeling. Conclusions: CA XIV plays a significant role in producing a normal retinal light response. Other isoforms of CA may provide functional redundancy in the absence of CA XIV.
Keywords: transgenics/knock-outs • enzymes/enzyme inhibitors • retinal degenerations: cell biology