Elevated aqueous endothelin-1 concentrations in advanced diabetic retinopathy

Hae Min Kang; Md Hasanuzzaman; So Won Kim; Hyoung Jun Koh; Sung Chul Lee

doi:10.1371/journal.pone.0268353

Elevated aqueous endothelin-1 concentrations in advanced diabetic retinopathy

PLoS One. 2022 May 11;17(5):e0268353. doi: 10.1371/journal.pone.0268353. eCollection 2022.

Authors

Hae Min Kang^{1

2}, Md Hasanuzzaman³, So Won Kim⁴, Hyoung Jun Koh⁴, Sung Chul Lee⁵

Affiliations

¹ Quantitative method, Harvard TH Chan School of Public Health, Boston, Massachusetts, United States of America.
² Catholic Kwandong University College of Medicine, Incheon, Republic of Korea.
³ Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁴ Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea.
⁵ Department of Ophthalmology, Konyang University Hospital, Daejeon, Republic of Korea.

Abstract

Purpose: Endothelin-1 (ET-1) is a potent vasoconstrictor which seems to be involved in the pathogenesis of diabetic retinopathy (DR). However, studies on intraocular ET-1 in DR have been limited. Thus, we investigated aqueous ET-1 levels in patients with DR.

Methods: A total 85 subjects were included in this prospective study. Those were classified into three groups: advanced DR group included those with severe nonproliferative DR or proliferative DR, whereas early DR group included those with mild nonproliferative DR or moderative nonproliferative DR. Those who underwent cataract surgery and had no concomitant ocular disease were included in the control group. Aqueous humor levels of ET-1 were obtained before intravitreal bevacizumab injection (IVB) and after 1 month for the DR patients, and at the time of cataract surgery for the control group.

Results: Advanced DR group included 40 eyes (47.1%), whereas early DR group did 19 eyes (22.4%), and control group (26 eyes, 30.5%). Mean aqueous ET-1 level was 10.1±4.1 pg/mL (6.0-21.0 pg/mL) in advanced DR group, 1.9±0.7 pg/mL (0.6-2.8 pg/mL) in early DR group, and 2.1±1.0 pg/mL (0.7-3.9 pg/mL) in control group (P < 0.001). Advanced DR group was further subdivided into severe nonproliferative DR (15 eyes, 12.8%) and proliferative DR (25 eyes, 34.3%). Mean aqueous ET-1 level was 10.1±4.3 pg/mL (6.0-20.1 pg/mL) in patients with severe nonproliferative DR, and 10.0±4.0 pg/mL (6.0-21.0 pg/mL) in those with proliferative DR (P = 0.928) at baseline. Mean ET-1 level at 1 month after intravitreal injection was 2.5±1.0 pg/mL (0.3-4.8 pg/mL) in patients with severe proliferative DR and 2.9±1.7 pg/mL (1.0-7.0 pg/mL) in those with proliferative DR (P = 0.443). Mean aqueous ET-1 level was significantly reduced in both groups (P < 0.001, respectively).

Conclusion: The mean aqueous ET-1 level was significantly higher in the eyes with advanced DR than those with early DR and the control group. The mean aqueous ET-1 level was significantly reduced after intravitreal injections in the advanced DR group. Based on our results, future studies on the exact role of ET-1 in the pathogenesis of DR and future implication for intervention would be helpful for managing DR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aqueous Humor
Bevacizumab / therapeutic use
Cataract*
Diabetes Mellitus*
Diabetic Retinopathy* / drug therapy
Endothelin-1
Humans
Prospective Studies

Substances

Endothelin-1
Bevacizumab

Grants and funding

This research is supported by a grant of the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI21C1251). None of the authors have a proprietary interest in this work. The sponsor or funding organization had no role in the design or conduct of this research.