Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration
PURPOSE: The growth of ocular neovascularization is regulated by a balance between stimulating and inhibiting growth factors. Somatostatin affects angiogenesis by inhibiting the growth hormone-insulin-like growth factor axis and also has a direct antiproliferative effect on human retinal endothelial cells. The purpose of our study is to investigate the expression of somatostatin receptor (sst) subtypes and particularly sst subtype 2A (sst2A) in normal human macula, and to study sst2A in different stages of age-related maculopathy (ARM), because of the potential anti-angiogenic effect of somatostatin analogues. METHODS: Sixteen eyes (10 enucleated eyes, 4 donor eyes, and 2 surgically removed choroidal neovascular [CNV] membranes) of 15 patients with eyes at different stages of ARM were used for immunohistochemistry. Formaldehyde-fixed paraffin-embedded slides were incubated with a polyclonal anti-human sst2A antibody. mRNA expression of five ssts and somatostatin was determined in the posterior pole of three normal human eyes by reverse transcriptase-polymerase chain reaction. RESULTS: The immunohistochemical expression of sstA in newly formed endothelial cells and fibroblast-like cells was strong in fibrovascular CNV membranes. mRNA of sst subtypes 1, 2A, and 3, as well as somatostatin, was present in the normal posterior pole; sst subtypes 4 and 5 were not detectable. CONCLUSIONS: Most early-formed CNV in ARM express sst2A. The presence of mRNA of sst subtype 2A was observed in normal human macula, and subtypes 1 and 3 and somatostatin are also present. sst2A receptors bind potential anti-angiogenic somatostatin analogues such as octreotide. Therefore, somatostatin analogues may be an effective therapy in early stages of CNV in ARM.
|Keywords||Adult, Aged, Aged, 80 and over, Choroidal Neovascularization/etiology/*genetics/metabolism, DNA Primers/chemistry, Female, Gene Expression, Humans, Immunoenzyme Techniques, Macula Lutea/metabolism, Macular Degeneration/*complications, Male, Middle aged, RNA, Messenger/*biosynthesis, Receptors, Somatostatin/biosynthesis/*genetics, Reverse Transcriptase Polymerase Chain Reaction|
Lambooij, A.C., Kuijpers, R.W.A.M., van Lichtenauer-Kaligis, E.G., Kliffen, M., Baarsma, G.S., van Hagen, P.M., & Mooy, C.M.. (2000). Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration. Investigative Ophthalmology & Visual Science. Retrieved from http://hdl.handle.net/1765/9421