Progenitor cell-derived factors enhance photoreceptor survival in rat retinal explants.

Abstract

Explantation of postnatal rat retinas is associated with degenerative events that show morphological similarities to human retinal degenerative disorders. The most evident morphological features are photoreceptor apoptosis involving caspase-3 and Müller cell activation. The purpose of the present study was to determine the content of protective factors in rat retinal progenitor cells and analyze the influence of the identified factors on the survival of photoreceptor cells and retinal gliosis. Tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF) were identified as putative beneficial factors, and their combined effect was examined in rat retinal explant cultures. Photoreceptor apoptosis was estimated by cell counts of cleaved caspase-3 and caspase-12 immunolabeled as well as TUNEL labeled cells. TIMP-1 and VEGF in combination significantly suppressed photoreceptor apoptosis involving caspase-3 activation. Cell counts of caspase-12 and TUNEL labeled photoreceptors showed no significant difference between the experiment and control retinas. TIMP-1 and VEGF appeared to have no effect on Müller cell activation as measured by GFAP and Ki-67 immunohistochemistry. Our data suggest that TIMP-1 and VEGF in combination promote the survival of photoreceptor cells in rat retinal explants, possibly by affecting a caspase-3 signaling pathway.

• Authors: Ingela Liljekvist-Soltic, Jenny Olofsson, Kjell Johansson
• Journal: Brain research (Brain Res) Vol. 1227 Pg. 226-33 (Aug 28 2008) ISSN: 0006-8993 [Print] Netherlands
• PMID: 18621034 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glial Fibrillary Acidic Protein
• Ki-67 Antigen
• Tissue Inhibitor of Metalloproteinase-1
• Vascular Endothelial Growth Factor A
• Caspase 12
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 12 (metabolism)
• Caspase 3 (metabolism)
• Cell Survival (drug effects)
• Cells, Cultured
• Female
• Glial Fibrillary Acidic Protein (metabolism)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Ki-67 Antigen (metabolism)
• Neuroglia (cytology, metabolism)
• Photoreceptor Cells (cytology, drug effects, metabolism)
• Pregnancy
• Rats
• Rats, Sprague-Dawley
• Retina (cytology, drug effects, metabolism)
• Stem Cells (cytology, metabolism)
• Tissue Culture Techniques
• Tissue Inhibitor of Metalloproteinase-1 (pharmacology)
• Vascular Endothelial Growth Factor A (pharmacology)