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Somatostatin receptor 2A expression in choroidal neovascularization secondary to age-related macular degeneration
A C Lambooij1, R W Kuijpers, E G van Lichtenauer-Kaligis
1Department of Ophthalmology, Erasmus University Rotterdam, The Netherlands. lambooji@gen.fgg.eur.nl
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.
Insights
Somatostatin receptor subtype 2A (sst2A) is present in normal macula and age-related maculopathy (ARM) choroidal neovascularization (CNV). This suggests somatostatin analogues may treat early ARM stages.
Area of Science:
- Ophthalmology
- Angiogenesis Research
- Molecular Biology
Background:
- Ocular neovascularization is regulated by growth factors.
- Somatostatin inhibits angiogenesis via growth hormone-insulin-like growth factor axis and has antiproliferative effects on retinal endothelial cells.
Purpose of the Study:
- Investigate somatostatin receptor (sst) subtype expression, particularly sst subtype 2A (sst2A), in normal human macula.
- Examine sst2A expression in different stages of age-related maculopathy (ARM).
- Assess the potential anti-angiogenic effect of somatostatin analogues in ARM.
Main Methods:
- Immunohistochemistry used on 16 eyes with varying stages of ARM, including choroidal neovascular (CNV) membranes.
- Slides incubated with anti-human sst2A antibody.
- Reverse transcriptase-polymerase chain reaction determined mRNA expression of five sst subtypes and somatostatin in three normal human eyes.
Main Results:
- Strong immunohistochemical expression of sst2A found in endothelial and fibroblast-like cells of fibrovascular CNV membranes.
- mRNA for sst subtypes 1, 2A, and 3, along with somatostatin, detected in the normal posterior pole.
- Sst subtypes 4 and 5 mRNA were not detectable in normal macula.
Conclusions:
- Most early-stage CNV in ARM express sst2A.
- Sst subtype 2A mRNA is present in normal human macula; subtypes 1 and 3 and somatostatin are also present.
- Sst2A receptors bind anti-angiogenic somatostatin analogues like octreotide, indicating potential therapeutic efficacy in early ARM stages.