1. Neuroprotection and neuroregeneration of retinal ganglion cells after intravitreal carbon monoxide release
- Author
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Stifter, Julia, Ulbrich, Felix, Goebel, Ulrich, Böhringer, Daniel, Lagrèze, Wolf Alexander, and Biermann, Julia
- Subjects
Retinal Ganglion Cells ,Male ,Macroglial Cells ,lcsh:Medicine ,Iris ,Biochemistry ,Rats, Sprague-Dawley ,Nerve Fibers ,GAP-43 Protein ,Animal Cells ,Cell Movement ,Coordination Complexes ,Tubulin ,Medicine and Health Sciences ,Phosphorylation ,lcsh:Science ,Cells, Cultured ,Neurons ,Carbon Monoxide ,Caspase 3 ,Microfilament Proteins ,NF-kappa B ,Neuroprotection ,Cell Motility ,Neuroprotective Agents ,Reperfusion Injury ,Intravitreal Injections ,Female ,Cellular Types ,Anatomy ,Mitogen-Activated Protein Kinases ,Neuroglia ,Research Article ,Ganglion Cells ,Ocular Anatomy ,Glial Cells ,Cell Migration ,Retina ,Ocular System ,Tubulins ,Glial Fibrillary Acidic Protein ,Animals ,HSP70 Heat-Shock Proteins ,cardiovascular diseases ,HSP90 Heat-Shock Proteins ,RNA, Messenger ,Tumor Necrosis Factor-alpha ,lcsh:R ,Calcium-Binding Proteins ,Biology and Life Sciences ,Afferent Neurons ,Proteins ,Cell Biology ,Axons ,Nerve Regeneration ,Cytoskeletal Proteins ,Cellular Neuroscience ,Astrocytes ,Eyes ,lcsh:Q ,sense organs ,Head ,Neuroscience ,Developmental Biology - Abstract
Purpose Retinal ischemia induces apoptosis leading to neurodegeneration and vision impairment. Carbon monoxide (CO) in gaseous form showed cell-protective and anti-inflammatory effects after retinal ischemia-reperfusion-injury (IRI). These effects were also demonstrated for the intravenously administered CO-releasing molecule (CORM) ALF-186. This article summarizes the results of intravitreally released CO to assess its suitability as a neuroprotective and neuroregenerative agent. Methods Water-soluble CORM ALF-186 (25 μg), PBS, or inactivated ALF (iALF) (all 5 μl) were intravitreally applied into the left eyes of rats directly after retinal IRI for 1 h. Their right eyes remained unaffected and were used for comparison. Retinal tissue was harvested 24 h after intervention to analyze mRNA or protein expression of Caspase-3, pERK1/2, p38, HSP70/90, NF-kappaB, AIF-1 (allograft inflammatory factor), TNF-α, and GAP-43. Densities of fluorogold-prelabeled retinal ganglion cells (RGC) were examined in flat-mounted retinae seven days after IRI and were expressed as mean/mm2. The ability of RGC to regenerate their axon was evaluated two and seven days after IRI using retinal explants in laminin-1-coated cultures. Immunohistochemistry was used to analyze the different cell types growing out of the retinal explants. Results Compared to the RGC-density in the contralateral right eyes (2804±214 RGC/mm2; data are mean±SD), IRI+PBS injection resulted in a remarkable loss of RGC (1554±159 RGC/mm2), p
- Published
- 2017