Yong Jie Qin1, Sun On Chan2, Hong Liang Lin3, Yu Qiao Zhang3, Bei Ting He4, Liang Zhang1, Hong Hua Yu1, Wai Kit Chu5, Chi Pui Pang5, Hong Yang Zhang6. 1. Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China. 2. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong. 3. Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China; Shantou University Medical College, Shantou, China. 4. 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. 5. Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong. 6. Department of Ophthalmology, Guangdong Eye Institute, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China. Electronic address: hy3005716@163.com.
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.
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.