Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger.
Vision is initiated by phototransduction in the outer retina by photoreceptors, whose high metabolic rate generates large CO2 loads. Inner retina cells then process the visual signal and CO2. The anion exchanger 3 gene (AE3/Slc4a3) encodes full-length AE3 (AE3fl) and cardiac AE3 (AE3c) isoforms, cat...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-09-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC1950688?pdf=render |
| _version_ | 1818961045293629440 |
|---|---|
| author | Bernardo V Alvarez Gregory S Gilmour Silvina C Mema Brent T Martin Gary E Shull Joseph R Casey Yves Sauvé |
| author_facet | Bernardo V Alvarez Gregory S Gilmour Silvina C Mema Brent T Martin Gary E Shull Joseph R Casey Yves Sauvé |
| author_sort | Bernardo V Alvarez |
| collection | DOAJ |
| description | Vision is initiated by phototransduction in the outer retina by photoreceptors, whose high metabolic rate generates large CO2 loads. Inner retina cells then process the visual signal and CO2. The anion exchanger 3 gene (AE3/Slc4a3) encodes full-length AE3 (AE3fl) and cardiac AE3 (AE3c) isoforms, catalyzing plasma membrane Cl-/HCO3- exchange in Müller (AE3fl) and horizontal (AE3c) cells. AE3 thus maintains acid-balance by removing photoreceptor-generated CO2 waste.We report that Slc4a3-/- null mice have inner retina defects (electroretinogram b-wave reduction, optic nerve and retinal vessel anomalies). These pathologic features are common to most human vitreoretinal degenerations. Immunobloting analysis revealed that Na+/HCO3- co-transporter (NBC1), and carbonic anhydrase II and CAXIV, protein expression were elevated in Slc4a3-/- mouse retinas, suggesting compensation for loss of AE3. TUNEL staining showed increased numbers of apoptotic nuclei from 4-6 months of age, in Slc4a3-/- mice, indicating late onset photoreceptor death.Identification of Slc4a3 as underlying a previously unrecognized cause of blindness suggests this gene as a new candidate for a subset of hereditary vitreoretinal retinal degeneration. |
| first_indexed | 2024-12-20T12:07:11Z |
| format | Article |
| id | doaj.art-e41e6646703545d5b21ca50f12ba97a3 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T12:07:11Z |
| publishDate | 2007-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e41e6646703545d5b21ca50f12ba97a32022-12-21T19:41:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-09-0129e83910.1371/journal.pone.0000839Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger.Bernardo V AlvarezGregory S GilmourSilvina C MemaBrent T MartinGary E ShullJoseph R CaseyYves SauvéVision is initiated by phototransduction in the outer retina by photoreceptors, whose high metabolic rate generates large CO2 loads. Inner retina cells then process the visual signal and CO2. The anion exchanger 3 gene (AE3/Slc4a3) encodes full-length AE3 (AE3fl) and cardiac AE3 (AE3c) isoforms, catalyzing plasma membrane Cl-/HCO3- exchange in Müller (AE3fl) and horizontal (AE3c) cells. AE3 thus maintains acid-balance by removing photoreceptor-generated CO2 waste.We report that Slc4a3-/- null mice have inner retina defects (electroretinogram b-wave reduction, optic nerve and retinal vessel anomalies). These pathologic features are common to most human vitreoretinal degenerations. Immunobloting analysis revealed that Na+/HCO3- co-transporter (NBC1), and carbonic anhydrase II and CAXIV, protein expression were elevated in Slc4a3-/- mouse retinas, suggesting compensation for loss of AE3. TUNEL staining showed increased numbers of apoptotic nuclei from 4-6 months of age, in Slc4a3-/- mice, indicating late onset photoreceptor death.Identification of Slc4a3 as underlying a previously unrecognized cause of blindness suggests this gene as a new candidate for a subset of hereditary vitreoretinal retinal degeneration.http://europepmc.org/articles/PMC1950688?pdf=render |
| spellingShingle | Bernardo V Alvarez Gregory S Gilmour Silvina C Mema Brent T Martin Gary E Shull Joseph R Casey Yves Sauvé Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger. PLoS ONE |
| title | Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger. |
| title_full | Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger. |
| title_fullStr | Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger. |
| title_full_unstemmed | Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger. |
| title_short | Blindness caused by deficiency in AE3 chloride/bicarbonate exchanger. |
| title_sort | blindness caused by deficiency in ae3 chloride bicarbonate exchanger |
| url | http://europepmc.org/articles/PMC1950688?pdf=render |
| work_keys_str_mv | AT bernardovalvarez blindnesscausedbydeficiencyinae3chloridebicarbonateexchanger AT gregorysgilmour blindnesscausedbydeficiencyinae3chloridebicarbonateexchanger AT silvinacmema blindnesscausedbydeficiencyinae3chloridebicarbonateexchanger AT brenttmartin blindnesscausedbydeficiencyinae3chloridebicarbonateexchanger AT garyeshull blindnesscausedbydeficiencyinae3chloridebicarbonateexchanger AT josephrcasey blindnesscausedbydeficiencyinae3chloridebicarbonateexchanger AT yvessauve blindnesscausedbydeficiencyinae3chloridebicarbonateexchanger |