Increased expression of Protein S in eyes with diabetic retinopathy and diabetic macular edema

Masahiko Sugimoto,Makoto Nakamura,Mineo Kondo,Corina N D’Alessandro-Gabazza,Esteban C Gabazza,Taro Yasuma,Hisanori Imai,Masaaki Toda

doi:10.1038/s41598-021-89870-5

Masahiko Sugimoto, Makoto Nakamura + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-89870-5

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Journal: Scientific Reports	Publication Date: May 17, 2021
Citations: 2	License type: open-access

Affiliation: Mie University, Kobe University

Abstract

Protein S (PS) is a multifunctional glycoprotein that ameliorates the detrimental effects of diabetes mellitus (DM). The aim of this study was to evaluate the distribution of PS in diabetic retinopathy (DR) and diabetic macular edema (DME). This was a study of 50 eyes with DM (37 with DME, 6 with proliferative DR, and 7 with no DR) and 19 eyes without DM. The level of PS was measured by enzyme immunoassay and was compared between eyes with or without DM, with or without DME, and with severe DME (≥ 350 μm) or mild DME (< 350 μm). We also performed immunohistopathologic evaluations of post-mortem eyes and the cystoid lesions excised during surgery. The aqueous free PS was significantly higher with DM (7.9 ± 1.2 ng/ml, P < 0.01) than without DM (6.1 ± 0.7). The aqueous free PS was significantly elevated with DME (8.2 ± 1.2, P < 0.05) compared to proliferative DR (7.0 ± 1.0) and no DR (7.0 ± 0.7). Eyes with severe DME had significantly higher aqueous free PS than mild DME (8.5 ± 1.3 vs. 7.7 ± 1.0, P < 0.05). Immunohistochemistry showed PS in the outer plexiform layer of the retina and cystoid lesion. The higher expression of PS with DR and DME suggests that PS is involved in their pathogenesis.

Highlights

There are approximately 400 million people with diabetes mellitus (DM) worldwide, and it has been estimated that the number will reach 600 million in 20 years[1]
Macular edema is the accumulation of extravascular fluid in the outer plexiform layer (OPL), the inner nuclear layer, and the Müller cells leading to localized expansion[15]
Byeon et al reported cysts within the outer plexiform and OPL that may be related to leaky vessels when examined by OCT19

Summary

Introduction

There are approximately 400 million people with diabetes mellitus (DM) worldwide, and it has been estimated that the number will reach 600 million in 20 years[1]. The presence of inflammation has led to a growing interest in developing inhibitors of the inflammation to treat these retinal disorders. In this context, the pro-inflammatory and angiogenic vascular endothelial growth factor (VEGF) is an important therapeutic target, and anti-VEGF agents are currently the first-line treatment for DME. PS circulates in the plasma in a free form and can complex with C4b-binding protein (C4BP), an inhibitor of the classic complement pathway Both the free form of PS (free PS) and complex form of PS exert anti-inflammatory activity. PS in complex with C4BP inhibits complement-mediated inflammation by localizing C4BP to the cell m embrane[9] These reported beneficial effects suggest the potential therapeutic application of PS for inflammatory diseases[10]. The role of PS in diabetic retinal complications has not been examined

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