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, Tolllike receptor 4, and interleukin-1b. 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 language | English (US) |
|---|---|
| Pages (from-to) | 1014-1025 |
| Number of pages | 12 |
| Journal | Diabetes |
| Volume | 68 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jan 1 2019 |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Monosodium urate contributes to retinal inflammation and progression of diabetic retinopathy. / Thounaojam, Menaka; Montemari, Annalisa; Powell, Folami Lamoke; Malla, Prerana; Gutsaeva, Diana Raisovna; Bachettoni, Alessandra; Ripandelli, Guido; Repossi, Andrea; Tawfik, Amany Mohamed; Martin, Pamela Moore; Facchiano, Francesco; Bartoli, Manuela.
In: Diabetes, Vol. 68, No. 5, 01.01.2019, p. 1014-1025.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Monosodium urate contributes to retinal inflammation and progression of diabetic retinopathy
AU - Thounaojam, Menaka
AU - Montemari, Annalisa
AU - Powell, Folami Lamoke
AU - Malla, Prerana
AU - Gutsaeva, Diana Raisovna
AU - Bachettoni, Alessandra
AU - Ripandelli, Guido
AU - Repossi, Andrea
AU - Tawfik, Amany Mohamed
AU - Martin, Pamela Moore
AU - Facchiano, Francesco
AU - Bartoli, Manuela
PY - 2019/1/1
Y1 - 2019/1/1
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, Tolllike receptor 4, and interleukin-1b. 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.
AB - 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, Tolllike receptor 4, and interleukin-1b. 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.
UR - http://www.scopus.com/inward/record.url?scp=85065109410&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065109410&partnerID=8YFLogxK
U2 - 10.2337/db18-0912
DO - 10.2337/db18-0912
M3 - Article
C2 - 30728185
AN - SCOPUS:85065109410
VL - 68
SP - 1014
EP - 1025
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 5
ER -