Increased Expression of Growth Hormone-Releasing Hormone in Fibrinous Inflammation of Proliferative Diabetic Retinopathy.

Yong Jie Qin, Sun On Chan, Hong Liang Lin, Yu Qiao Zhang, Bei Ting He, Liang Zhang, Hong Hua Yu, Wai Kit Chu, Chi Pui Pang, Hong Yang Zhang

Journal: American journal of ophthalmology 2020;215():81-90

PMID: 32061756

Full Text on Elsevier Science View on PubMed

Abstract

PURPOSE

To investigate the involvement of growth hormone-releasing hormone (GHRH) - growth hormone (GH) signaling in pathogenesis of proliferative diabetic retinopathy (PDR).

DESIGN

Experimental laboratory study.

METHODS

Vitreous humor, aqueous humor, and serum were obtained from 36 eyes of 36 patients with or without type 2 diabetes from 2017 to 2019. For histologic examination, 6 fibrovascular membranes were excised from eyes with active PDR. Three fibrovascular membranes were excised from nondiabetic patients with proliferative vitreoretinopathy (PVR) as controls.

RESULTS

In PDR, the fibrovascular tissues consisted of a mature region containing fibrocytes, and an immature region populated by abundant polymorphonuclear leukocytes in a fibrinogen meshwork. Clusters of leukocytes were found adhering to the vascular walls. In PVR, no fibrinogen and polymorphonuclear leukocyte was observed in the fibrovascular membranes. The levels of GHRH and GH in PDR were significantly increased (P < .001), with 1.8-fold and 72.8-fold in vitreous humor, and 2-fold and 4.9-fold in aqueous humor, respectively, when compared with corresponding levels in controls. No significant difference was detected for insulin-like growth factor-1. Immunohistochemistry showed intense expression of GHRH and its receptor GHRH-R in polymorphonuclear leukocytes, vascular endothelial cells, and fibrocytes in fibrovascular membranes of PDR. GHRH staining was not detectable in infiltrating cells within the fibrovascular membrane of PVR.

CONCLUSIONS

These findings reveal a possible involvement of GHRH/GHRH-R in fibrinous inflammation that might contribute to the formation of fibrovascular membrane in PDR through mediating activities of leukocytes, vascular endothelial cells, and fibrocytes. Targeting GHRH/GHRH-R may be considered as a potential therapeutic approach for the treatment of PDR.

Address: Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China.; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong.; Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China; Shantou University Medical College, Shantou, China.; Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China; School of Medicine, South China University of Technology, Guangzhou, China.; Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong.; Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China. Electronic address: [email protected].

DOI: 10.1016/j.ajo.2020.02.006

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MeSH Terms: Adult, Aged, Aqueous Humor, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Endothelium, Vascular, Enzyme-Linked Immunosorbent Assay, Female, Fibroblasts, Growth Hormone-Releasing Hormone, Humans, Inflammation, Male, Middle Aged, Neutrophils, Receptors, Neuropeptide, Receptors, Pituitary Hormone-Regulating Hormone, Vitreous Body