title: Vascular endothelial growth factor in the ischemic retina and its regulation by somatostatin.
abstract: In a retinal ischemic ex vivo model, we have reported protective effects of somatostatin (SRIF) receptor 2 (sst(2) ). As an ischemic condition not only causes cell death but also induces a vascular response, we asked whether vascular endothelial growth factor (VEGF) is altered in this model and whether its expression, release or localization are affected by sst(2) activation. Ex vivo retinas of wild-type (WT) and sst(1) KO mice (which over-express sst(2) ) were incubated in ischemic conditions with SRIF, octreotide (OCT) or a VEGF trap. Ischemia in WT retinas caused increase of VEGF release and decrease of VEGF mRNA. Both effects were counteracted by SRIF or OCT. VEGF immunoreactivity was in retinal neurons and scarcely in vessels. Ischemia caused a significant shift of VEGF immunoreactivity from neurons to vessels. The increase of vascular VEGF was reduced in sst(1) KO retinas and in WT retinas treated with SRIF or OCT. VEGF trap also limited this increase, demonstrating that vascular VEGF was of extracellular origin. Together, the data show a VEGF response to ischemia, in which VEGF released by damaged neurons reaches the retinal capillaries. The activation of sst(2) protects neurons from ischemic damage, thereby limiting VEGF release and the VEGF response.
authors.affiliation: Department for Innovation in Biological, Agro-food and Forest systems, University of Tuscia, Viterbo, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Cervia
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Catalani
authors.forename: Massimo
authors.initials: M
authors.lastname: Dal Monte
authors.forename: Giovanni
authors.initials: G
authors.lastname: Casini
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D066298:In Vitro Techniques; D007511:Ischemia / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015282:Octreotide / Q000009:adverse effects; D012333:RNA, Messenger; D017481:Receptors, Somatostatin / Q000172:deficiency; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D042461:Vascular Endothelial Growth Factor A; C570770:somatostatin receptor 1, mouse; D013004:Somatostatin; D015282:Octreotide