APX‑115A, a pan‑NADPH oxidase inhibitor, reduces the degree and incidence rate of dry eye in the STZ‑induced diabetic rat model

Min Hye Noh; Dong Kun Lee; Yeong Seok Kim; Hye Young Kim; Sung Hwan Moon; Sang Youb Han; Dae Young Hur

doi:10.3892/etm.2023.11893

APX‑115A, a pan‑NADPH oxidase inhibitor, reduces the degree and incidence rate of dry eye in the STZ‑induced diabetic rat model

Exp Ther Med. 2023 Mar 17;25(5):194. doi: 10.3892/etm.2023.11893. eCollection 2023 May.

Authors

Min Hye Noh¹, Dong Kun Lee², Yeong Seok Kim¹, Hye Young Kim¹, Sung Hwan Moon³, Sang Youb Han⁴, Dae Young Hur¹

Affiliations

¹ Department of Anatomy and Tumor Immunology, Inje University College of Medicine, Busan 47392, Republic of Korea.
² Department of Otolaryngology-Head and Neck Surgery, Dong-A University College of Medicine, Busan 49201, Republic of Korea.
³ AptaBio Therapeutics Incorporation, Yongin, Gyeonggi 16954, Republic of Korea.
⁴ Department of Internal Medicine, Inje University Ilsan-Paik Hospital, Goyang, Gyeonggi 10380, Republic of Korea.

Abstract

Dye eye disease (DED) is a common ocular disorder in patients with diabetes. It has been reported that APX-115A, a pan-nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase inhibitor, has an apoptosis-inducing effect on Epstein-Barr virus-infected retinal epithelial cells, but its effects in DED are poorly understood. Therefore, a rat model of diabetes was used in the present study to investigate whether APX-115A has an impact on DED in diabetic rats. A diabetic model was established in male Sprague Dawley rats via the intraperitoneal injection of streptozotocin. The eyeballs of the rats were treated with a solution containing APX-115A or a saline control. Tear secretion was measured with the phenol red thread tear test, and the morphology of the eyeball and lacrimal gland tissues was determined using hematoxylin and eosin staining. In addition, localization of NAPDH oxidase 2 (NOX2) in the eyeball and lacrimal gland tissues was detected by immunohistochemistry. The APX-115A treatment had no effect on body weight, blood glucose level or the size of the lacrimal glands. However, morphological changes, namely intracellular vacuoles and acinar atrophy, were observed in the lacrimal glands of the diabetic rats, and APX-115A treatment attenuated these changes. Immunohistochemistry revealed that NOX2 expression was decreased in the lacrimal glands of the diabetic rats, and APX-115A treatment did not attenuate the reduction in NOX2. The corneas of the diabetic rats treated with APX-115A exhibited no change in thickness but had lower NOX2 expression levels compared with those of the control diabetic rats. APX-115A also increased tear secretion and ameliorated the histological changes associated with diabetes. Furthermore, the NOX2 expression levels in the corneas of the diabetic rats treated with APX-115A were restored to the levels observed in normal rats. These findings suggest that APX-115A has potential as a therapeutic agent for DED.

Keywords: NOX inhibitor; NOX2; VEGF; diabetes mellitus; dry eye syndrome.

Grants and funding

Funding: The present study was supported by a 2019 Inje University research grant.