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Felicity de Cogan, Jenna ONeill, Richard J Blanch, Robert A H Scott, Ann Logan; The role of Decorin in ocular ageing and disease. Invest. Ophthalmol. Vis. Sci. 2014;55(13):400. doi: https://doi.org/.
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Pro-fibrotic TGF-β isoforms initiate intraocular scarring after surgery and also are implied in the aetiology of ocular hypertension (OHT) and primary open angle glaucoma (POAG), diseases that are associated with ocular aging. The intravitreal proteoglycan Decorin has important physiological roles in dampening cytokine responses in the retina and sequesters TGF-β to regulate its bioactivity. In this study we investigated the relationship of Decorin and TGF-β bioactivity within the eye. Our hypothesis is that loss of Decorin during ageing leads to increased TGF-β bioactivity, which increases the risk of subsequent OHT/POAG and proliferative vitreoretinopathy (PVR) after retinal detachment.
Vitreal samples were collected from patients presenting with rhegmatogenous retinal detachments, macula holes and ocular trauma. Patients were excluded if they were under 10 years of age and had had previous retinal surgery. The vitreous was collected during surgical vitrectomy and centrifuged, the supernatant frozen at -80 °C and subsequently analysed by ELISA for the presence of active TGF-β2, latent TGF-β2 and Decorin.
Intravitreal Decorin significantly decreased with patient age. Patients under 40 years had a Decorin concentration of 1729±295 pg/mL, which reduced to 321±204 pg/mL by the age of 50, with levels remaining low for all patients above this age. TGF-β2 exists in 2 forms, active and latent, in its active form TGF-β2 is highly bioactive and is linked to fibrosis and ocular degeneration. Although the levels of total TGF-β2 didn’t change between age groups, the ratio of active TGF-β2 to total TGF-β2 was significantly enhanced with increasing patient age. Hence, patients under 40 years had 45.07±2.81 % of the TGF-β2 in the active form whereas patients above 50 years had 86.68±3.2 % of the TGF-β2 in the active form. The increased ratio of active TGF-β2 to latent TGF-β2 levels were inversely correlated with the decrease in Decorin in the vitreous of patients.
Intravitreal Decorin levels decline with age irrespective of underlying pathology. This decrease is correlated with an increase in levels of bioactive TGF-β2. The results imply a causal link between Decorin decline with age, TGF-β2 activation and the aetiology of fibrotic pathologies. Targeted supplementation of the eyes of older patients with Decorin may reduce age related diseases associated with intraocular fibrosis like OHT/POAG and post-retinal detachment PVR.
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