Elevated Expression of GHRH in Fibrinous Inflammation of PDR
By Lynda Seminara
Selected By: Richard K. Parrish II, MD
American Journal of Ophthalmology, July 2020
Early in the pathogenesis of diabetic retinopathy (DR), immune cells become trapped in retinal capillaries, leading to retinal hypoxia, neovascularization, and eventually fibrovascular membranes (FVMs). Similarly, FVM development at the vitreoretinal interface is characteristic of proliferative diabetic retinopathy (PDR).
In a first-of-its-kind study, Qin et al. investigated whether the formation of FVMs in PDR also is linked to sustained inflammation. They found fibrinous inflammation in the FVMs of patients with active PDR. In addition, the authors found increased levels of growth hormone‒releasing hormone (GHRH) and its receptor (GHRH-R) in the vitreous humor and their rich expression in polymorphonuclear leukocytes and other cells in PDR.
For this experimental study, the authors sampled vitreous humor, aqueous humor, and serum from the eyes of 36 patients: 12 with type 2 diabetes, 12 with PDR, and 12 with nondiabetic proliferative vitreoretinopathy (PVR) due to retinal detachment. The latter served as controls. Age and sex distributions were similar for the three groups, but mean levels of hemoglobin A1c and fibrinogen were much higher in patients with type 2 diabetes or PDR than in controls.
Six FVM samples were obtained from patients with PDR and three from patients with PVR. Histologic evaluation showed the following:
- In patients with PDR, the FVMs were composed of a mature region containing differentiated fibrocytes and rich blood vessels and an immature region with macrophage-like cells, numerous infiltrating polymorphonuclear leukocytes, and a fibrinogen-rich network.
- In those with PVR, the mature region of FVMs contained primarily differentiated fibrocytes, whereas the immature region contained mononuclear cells but no polymorphonuclear cells or fibrinogen-rich lattice.
With respect to GHRH and growth hormone (GH), the levels in PDR eyes were much higher in the vitreous humor (1.8-fold and 72.8-fold, respectively) and aqueous humor (2-fold and 4.9-fold, respectively) than in control eyes. In patients with type 2 diabetes, GH but not GHRH was elevated. Immunostaining for expression patterns in FVMs revealed GHRH and GHRH-R in polymorphonuclear leukocytes and vascular endothelial cells of patients with PDR. GHRH-R also was seen in fibrocytes of this group. Moreover, both were observed in polymorphonuclear cells that appeared to penetrate blood vessels.
In patients with PVR, GHRH-R was seen in fibrocytes and infiltrating mononuclear cells, and GHRH was detected in fibrocytes but not in infiltrating immune cells.
The authors hypothesize that GHRH and GHRH-R are involved in fibrinous inflammation in PDR by mediating the activities of polymorphonuclear leukocytes, vascular endothelial cells, and fibrocytes—potentially leading to generation and remodeling of FVMs. Further research may pave the way for therapies targeting GHRH and its receptor.
The original article can be found here.