Spatial and temporal distribution of growth factors and their receptors in diabetic retinopathy

Smith, Gillian M. 2007. Spatial and temporal distribution of growth factors and their receptors in diabetic retinopathy. PhD Thesis, Cardiff University.

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Abstract

PURPOSE To determine the distribution of vascular endothelial growth factor (VEGF) isoforms, angiopoietins (Ang-1 and -2) and their receptors, tumour necrosis factor alpha (TNF-a), pigment epithelium-derived factor (PEDF), and caveolin family members (Cav-1, -2, and -3) in non-diabetic retinas and diabetic retinas at different stages of diabetic retinopathy. METHODS Human eyes, obtained at post-mortem, were divided into those without diabetes and those with diabetes. Diabetic retinas were examined by microscopy and categorised as either nonlasered with no obvious features of retinopathy, non-lasered with intraretinal changes (microaneurysms, exudates etc.) but no evidence of proliferative diabetic retinopathy (PDR), diabetic with proliferative retinopathy, and those which had received scatter laser photocoagulation therapy and who no longer had evidence of PDR. Immunohistochemistry was used to determine the localisation of growth factors and caveolins in diabetic and control retinas, as well as in excised PDR membranes. RESULTS There appeared to be both temporal and spatial changes in the staining pattern for each growth factor in diabetic retina which correlated with the stage of disease progression. Apart from Ang-2 and PEDF, immunostaining was raised in diabetic retina as compared to nondiabetic retina. Immunostaining was apparent in endothelial cells and the perivascular cells of the vessels. Immunostaining was also apparent within specific retinal layers for VEGF-A, VEGF-C, VEGFR’s, Ang-2, Tie-2, TNF-a, PEDF, and caveolin 1, -2, and -3. CONCLUSION These data suggest a role for both angiogenic factors and anti-angiogenic factors and the caveolins in the pathogenesis of diabetic retinopathy, possibly by acting synergistically to mediate a wide range of cellular responses culminating in the formation of a fibrovascular membrane. Therapeutic intervention to the VEGF and Tie-2 receptor, and possibly stimulation of the PEDF signalling, pathways may prove useful for the treatment of PDR.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Optometry and Vision Sciences
Subjects:	R Medicine > RE Ophthalmology
ISBN:	9781303210167
Date of First Compliant Deposit:	30 March 2016
Last Modified:	19 Mar 2016 23:30
URI:	https://orca.cardiff.ac.uk/id/eprint/54675

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