Abstract
Abstract: :
Purpose: Vascular endothelial growth factor-A (VEGF-A) is involved in increased permeability and angiogenesis in diabetic retinopathy and age-related macular degeneration, and hence VEGF-A is considered as potential target for therapeutic strategies against these diseases. However, physiological functions of the VEGF family in normal retina are unclear and may interfere with such systemic therapies. In pathological conditions, high levels of expression of VEGF receptors VEGFR-1, VEGFR-2 and VEGFR-3 accompany VEGF activity. Therefore, we investigated normal human and monkey retinal tissues for expression of these receptors. Methods: In retinas of 18 eyes of healthy donor eyes, and 2 healthy monkey eyes, immunohistochemical staining methods were applied using monoclonal antibodies (mAbs) against the three VEGFRs, and anti-CD31 to identify blood vessels. Results: Only staining of VEGFR-1 was ubiquitously observed in retinal microvascular walls. Outside the vasculature, variable diffuse staining of VEGFR-1 and VEGFR-2 was present in neural or glial elements of the ganglion cell layer, the inner plexiform and nuclear layers, and the outer plexiform layer. Staining of VEGFR-3 was observed in the inner plexiform and nuclear layer and in a distinct pearl necklace-like configuration in the outer plexiform layer, a pattern highly suggestive for staining of synaptic complexes of cone-photoreceptors. Conclusion: These findings indicate that VEGFRs have specific distribution patterns in the normal human retina, suggesting physiological functions of VEGFs in and outside the vasculature, which may be disturbed by systemic or local anti-VEGF therapy. Further investigation is required to determine the exact cellular localization of the VEGFRs.
Keywords: 554 retina • 423 growth factors/growth factor receptors