Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy

Menaka C Thounaojam, Annalisa Montemari, Folami L Powell, Prerana Malla, Diana R Gutsaeva, Alessandra Bachettoni, Guido Ripandelli, Andrea Repossi, Amany Tawfik, Pamela M Martin, Francesco Facchiano, Manuela Bartoli

Research output: Contribution to journalArticle

Abstract

We have investigated the contributing role of monosodium urate (MSU) to the pathological processes associated with the induction of diabetic retinopathy (DR). In human postmortem retinas and vitreous from donors with DR, we have found a significant increase in MSU levels that correlated with the presence of inflammatory markers and enhanced expression of xanthine oxidase. The same elevation in MSU levels was also detected in serum and vitreous of streptozotocin-induced diabetic rats (STZ-rats) analyzed at 8 weeks of hyperglycemia. Furthermore, treatments of STZ-rats with the hypouricemic drugs allopurinol (50 mg/kg) and benzbromarone (10 mg/kg) given every other day resulted in a significant decrease of retinal and plasma levels of inflammatory cytokines and adhesion factors, a marked reduction of hyperglycemia-induced retinal leukostasis, and restoration of retinal blood-barrier function. These results were associated with effects of the hypouricemic drugs on downregulating diabetes-induced levels of oxidative stress markers as well as expression of components of the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome such as NLRP3, Toll-like receptor 4, and interleukin-1β. The outcomes of these studies support a contributing role of MSU in diabetes-induced retinal inflammation and suggest that asymptomatic hyperuricemia should be considered as a risk factor for DR induction and progression.

Original languageEnglish
Pages (from-to)1014-1025
Number of pages12
JournalDiabetes
Volume68
Issue number5
DOIs
Publication statusPublished - May 2019

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Diabetic Retinopathy
Uric Acid
Inflammation
Streptozocin
Hyperglycemia
Benzbromarone
Leukostasis
Blood-Retinal Barrier
Inflammasomes
Hyperuricemia
Allopurinol
Toll-Like Receptor 4
Xanthine Oxidase
Pathologic Processes
Interleukin-1
Pharmaceutical Preparations
Retina
Oxidative Stress
Down-Regulation
Outcome Assessment (Health Care)

Cite this

Thounaojam, M. C., Montemari, A., Powell, F. L., Malla, P., Gutsaeva, D. R., Bachettoni, A., ... Bartoli, M. (2019). Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy. Diabetes, 68(5), 1014-1025. https://doi.org/10.2337/db18-0912

Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy. / Thounaojam, Menaka C; Montemari, Annalisa; Powell, Folami L; Malla, Prerana; Gutsaeva, Diana R; Bachettoni, Alessandra; Ripandelli, Guido; Repossi, Andrea; Tawfik, Amany; Martin, Pamela M; Facchiano, Francesco; Bartoli, Manuela.

In: Diabetes, Vol. 68, No. 5, 05.2019, p. 1014-1025.

Research output: Contribution to journalArticle

Thounaojam, MC, Montemari, A, Powell, FL, Malla, P, Gutsaeva, DR, Bachettoni, A, Ripandelli, G, Repossi, A, Tawfik, A, Martin, PM, Facchiano, F & Bartoli, M 2019, 'Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy', Diabetes, vol. 68, no. 5, pp. 1014-1025. https://doi.org/10.2337/db18-0912
Thounaojam MC, Montemari A, Powell FL, Malla P, Gutsaeva DR, Bachettoni A et al. Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy. Diabetes. 2019 May;68(5):1014-1025. https://doi.org/10.2337/db18-0912
Thounaojam, Menaka C ; Montemari, Annalisa ; Powell, Folami L ; Malla, Prerana ; Gutsaeva, Diana R ; Bachettoni, Alessandra ; Ripandelli, Guido ; Repossi, Andrea ; Tawfik, Amany ; Martin, Pamela M ; Facchiano, Francesco ; Bartoli, Manuela. / Monosodium Urate Contributes to Retinal Inflammation and Progression of Diabetic Retinopathy. In: Diabetes. 2019 ; Vol. 68, No. 5. pp. 1014-1025.
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AU - Gutsaeva, Diana R

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AU - Tawfik, Amany

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N2 - We have investigated the contributing role of monosodium urate (MSU) to the pathological processes associated with the induction of diabetic retinopathy (DR). In human postmortem retinas and vitreous from donors with DR, we have found a significant increase in MSU levels that correlated with the presence of inflammatory markers and enhanced expression of xanthine oxidase. The same elevation in MSU levels was also detected in serum and vitreous of streptozotocin-induced diabetic rats (STZ-rats) analyzed at 8 weeks of hyperglycemia. Furthermore, treatments of STZ-rats with the hypouricemic drugs allopurinol (50 mg/kg) and benzbromarone (10 mg/kg) given every other day resulted in a significant decrease of retinal and plasma levels of inflammatory cytokines and adhesion factors, a marked reduction of hyperglycemia-induced retinal leukostasis, and restoration of retinal blood-barrier function. These results were associated with effects of the hypouricemic drugs on downregulating diabetes-induced levels of oxidative stress markers as well as expression of components of the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome such as NLRP3, Toll-like receptor 4, and interleukin-1β. The outcomes of these studies support a contributing role of MSU in diabetes-induced retinal inflammation and suggest that asymptomatic hyperuricemia should be considered as a risk factor for DR induction and progression.

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