Mapping cation entry in photoreceptors and inner retinal neurons during early degeneration in the P23H-3 rat retina
| Autor: | Yuan, Zhu, Stuti, Misra, Stuti, Mistra, Lisa, Nivison-Smith, Monica L, Acosta, Erica L, Fletcher, Michael, Kalloniatis |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Retinal degeneration
Opsin Rhodopsin Silver Staining genetic structures Agmatine Proline Physiology Apoptosis Nerve Tissue Proteins Gene mutation Biology Retina Rats Sprague-Dawley Retinitis pigmentosa medicine Animals Humans Histidine Photoreceptor Cells Neurons Retinal Degeneration Glutamate receptor Age Factors Gene Expression Regulation Developmental medicine.disease eye diseases Sensory Systems Cell biology Rats medicine.anatomical_structure Mutation Ionotropic glutamate receptor sense organs Rats Transgenic Neuroscience Ionotropic effect |
| Zdroj: | Visual neuroscience. 30(3) |
| ISSN: | 1469-8714 |
| Popis: | The proline-23-histidine line 3 (P23H-3) transgenic rat carries a human opsin gene mutation leading to progressive photoreceptor loss characteristic of human autosomal dominant retinitis pigmentosa. The aim of the present study was to evaluate neurochemical modifications in the P23H-3 retina as a function of development and degeneration. Specifically, we investigated the ion channel permeability of photoreceptors by tracking an organic cation, agmatine (1-amino-4-guanidobutane, AGB), which permeates through nonspecific cation channels. We also investigated the activity of ionotropic glutamate receptors in distinct populations of bipolar, amacrine, and ganglion cells using AGB tracking in combination with macromolecular markers. We found elevated cation channel permeation in photoreceptors as early as postnatal day 12 (P12) suggesting that AGB labeling is an early indicator of impending photoreceptor degeneration. However, bipolar, amacrine, or ganglion cells displayed normal responses secondary to ionotropic glutamate receptor activation even at P138 when about one half of the photoreceptor layer was lost and apoptosis and gliosis were observed. These results suggest that possible therapeutic windows as downstream neurons in inner retina appear to retain normal function with regard to AGB permeation when photoreceptors are significantly reduced but not lost. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|