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Kousuke Noda, Miyuki Murata, Wataru Saito, Atsuhiro Kanda, Susumu Ishida; Accumulation of Acrolein-conjugated Protein in the Vitreous Fluid of Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2514.
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Acrolein (ACR) is a highly reactive unsaturated aldehyde that readily forms conjugates with proteins, and has been recognized as an exogenous pollutant causing pulmonary disorders. However, it has recently been shown that ACR is also produced endogenously as a result of polyamine metabolism mediated by amine oxidases and plays a role in cell toxicity and oxidative stress. We previously reported that semicarbazide-sensitive amine oxidase (SSAO) increased and correlated with oxidative stress in the vitreous of patients with proliferative diabetic retinopathy (PDR); however, its role in the pathogenesis of PDR has remained unclear. In this study, we measured the concentration of acrolein-conjugated protein, Nε-(3-formyl-3,4-dehydropiperidino) lysine adduct (FDP-Lys), in the vitreous fluid samples of proliferative diabetic retinopathy (PDR) and sought to explore the link between SSAO and ACR in eyes with PDR.
Vitreous samples were collected from 12 eyes of 12 patients with PDR (7 males and 5 females; mean age, 58.2±4.1 y/o), who underwent pars plana vitrectomy for prolonged vitreous hemorrhage and tractional retinal detachment involving macular lesions. For a control, vitreous samples were obtained from 9 eyes of 9 patients with non-diabetic ocular diseases (non-PDR): epiretinal membrane and idiopathic macular hole (4 males and 5 females; mean age, 68.4±3.1 y/o). Vitreous levels of FDP-Lys and semicarbazide-sensitive amine oxidase (SSAO) were measured by ELISA.
The FDP-Lys was detectable in all the PDR and non-PDR vitreous samples and was significantly elevated in the vitreous fluids of PDR patients (11.2±0.8nmol/ml) compared with those of non-PDR patients (8.8±0.3nmol/ml, P<0.05). In addition, protein levels of SSAO showed approximately 8.0-fold increase in the vitreous fluids of PDR patients when compared with those of non-PDR patients (9.4±1.4ng/ml vs 1.2±0.2ng/ml, P<0.01). Furthermore, the level of FDP-Lys showed a moderate correlation with SSAO concentration in the vitreous samples of PDR patients (ρ=0.67, P<0.05).
The current data showed that ACR-conjugated protein was increased and correlated with SSAO in the vitreous fluid of patients with PDR, suggesting that SSAO plays a role in the production of ACR.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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