Abstract
Purpose: :
To evaluate the role of somatostatin (SS) and its receptors 1–5 (SSTR1–5) in the lacrimal apparatus and at the ocular surface.
Methods: :
Recent investigations revealed the presence of somatostatin in the excretory system of the lacrimal gland and in tear fluid. To get deeper insights into a possible role of SS at the ocular surface and in the lacrimal system the distribution pattern of SS and its receptors 1–5 was investigated by means of RT–PCR, Western–blot analysis, dot blot analysis and immunohistochemistry in lacrimal gland, tear fluid, conjunctiva, cornea, nasolacrimal duct epithelium as well as conjunctival and corneal epithelial cell lines. Cell culture experiments with SV40–immortalized human corneal epithelial (HCE) cells and a conjunctival (HCjE, IOBA–NHC) epithelial cell line were undertaken to analyze a possible impact of SS on the activation of MAP–kinases ERK1/2 and a possible influence of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) on SSTR regulation.
Results: :
The results by RT–PCR, Western blot, dot blot and immunohistochemistry confirmed the presence of SS in lacrimal gland and tear fluid. Expression of SSTRs1–5 was visible in lacrimal gland, whereas immunohistochemistry detected only SSTRs 1, 2 and 5. These latter receptors were also detected in conjunctiva, cornea, nasolacrimal ducts as well as corneal and conjunctival epithelial cell lines (except SSTR5) by RT–PCR and immunohistochemistry. Western blot analysis confirmed the presence of SSTR2 in all investigated tissues. Cell culture experiments with HCE revealed that SS alone had nearly no effect on ERK1/2 phosphorylation but a strongly increasing activation was seen when SS was used in combination with VEGF or EGF. This effect was further enhanced if SS was replaced by SS analogues like octreotid or L054.522. Moreover, stimulation with different concentrations of recombinant VEGF led to induction of SSTR2 in HCjE.
Conclusions: :
These primary data support an autocrine and paracrine role of SS in the lacrimal system and at the ocular surface and may implicate a role of SS in corneal angiogenesis.
Keywords: cornea: tears/tear film/dry eye • lacrimal gland • cornea: basic science